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TPV?: should transcription include reverse transcription? #5589

Closed gocentral closed 8 years ago

gocentral commented 15 years ago

it is The synthesis of either RNA on a template of DNA or DNA on a template of RNA.

should transcription include reverse transcription? at one point, I think transcription used to be an RNA metabolic process, but now it isn't, I'm guessing this is why?

Intuitively (possibly wrongly) it seems that transcription and "reverse transcription" should be separate sibling terms. For example reverse transcription isn't part of 'gene expression' is it?

Reported by: ValWood

Original Ticket: "geneontology/ontology-requests/5607":https://sourceforge.net/p/geneontology/ontology-requests/5607

gocentral commented 15 years ago

Original comment by: ValWood

gocentral commented 15 years ago

"Forward" and reverse transcription are separate sibling terms:

transcription GO:0006350 [i] transcription, DNA-dependent GO:0006351 [i] transcription, RNA-dependent GO:006410

so that part is OK.

It looks like we ought to merge transcription, RNA-dependent (GO:006410) and RNA-dependent DNA replication (GO:0006278), because I can't see any difference, and the merged term maybe shouldn't be under DNA replication (and 'DNA synthesis' could be a term rather than a related synonym for DNA replication).

And I don't know whether reverse transcription should be considered part of gene expression; if not, we can switch to using GO:006351 as part of gene exp instead.

I'll leave this open for a few days so the USians have a chance to see it and comment.

m

Original comment by: mah11

gocentral commented 15 years ago

Transcribed (not in the mol biol sense!) from email exchange (read down):

== Harold, 01 Dec 2008 11:33:57 -0500 == Hmm, from the def of 64101, the term name really doesn't fit, since to me, RNA -dependent transcription would be a process whereby an RNA template is transcribed to create another RNA molecule. As it's defined, it is "reverse" transcription. Based on the def, I would vote to merge them.

== David, 01 Dec 2008 11:40:19 -0500 == I agree with Harold. Reverse transcription refers to the process of reversing the transcription process, not a type of transcription.

== Midori, 1 Dec 2008 16:46:06 +0000 (GMT) == Wait, I'm confused now about what you guys favor. RNA-dependent synthesis of RNA isn't transcription at all; it's RNA replication.

Transcription is the interconversion of DNA and RNA by synthesizing one on a template made of the other. Synthesis of RNA on a DNA template is considered "forward" because it's by far the more common direction.

== Harold, 01 Dec 2008 12:56:10 -0500 == It's all in what the copy is used for I think:

I suppose an RNA dependent RNA polymerase vs a DNA dependent RNA polymerase... vs ....

In the case of some single strand viral genomes:

A negative-sense ssRNA virus genome is copied by an RNA polymerase to form positive-sense RNA. This means that the virus must bring along with it the RNA-dependent RNA polymerase enzyme. The positive-sense RNA molecule then acts as viral mRNA, which is translated into proteins by the host ribosomes.

A positive-sense ssRNA viruse genome is directly used as an mRNA, making a single protein which is modified by host and viral proteins to form the various proteins needed for replication. One of these includes RNA-dependent RNA polymerase, which copies the viral RNA to form a double-stranded replicative form, in turn this directs the formation of new virions.

Both processes use an RNA template and make an RNA. one is transcription, the other replication.

== Karen, 1 Dec 2008 15:15:41 -0800 (PST) == Hmmm, a tricky question...

Reading through the whole thread so far, I have several comments.

  1. Based on the current defs of "RNA-dependent DNA replication" (which includes the phrase 'RNA-dependent DNA polymerases (e.g. reverse transcriptase)' and of "transcription, RNA-dependent" which has 'reverse transcriptase' as a synonym, these two terms do seem to be identical.

However, it seems to me that the reverse transcription (txn) step is only half of "RNA-dependent DNA replication" because reverse txn only makes a ssDNA copy. This ssDNA then serves as the template for production of dsDNA (going off my old biology book). So, perhaps the def of "RNA-dependent DNA replication" needs to be broader to encompass the whole process, and "transcription, RNA-dependent" could have a part_of relationship to such a redefined/new term.

  1. Harold's example of "A negative-sense ssRNA virus genome is copied by an RNA polymerase to form positive-sense RNA" is currently outside the scope of the question at hand, since this is not included in either form of transcription represented in GO by current defs:
    • txn, RNA-dependent = ssDNA copy from RNA template
    • txn, DNA-dependent = ssRNA copy from DNA template

I'm definitely not an expert on all the ways viruses can do things, so it may be that we need to represent making a ssRNA copy from an RNA template, but this is currently not included in the def of "txn, RNA-dependent".

  1. While I see where Harold is going in the idea that it's "all in what the copy is used for", I'm not sure that we can use this to distinguish. In terms of how enzymologists think of reverse transcriptase, it's the enzyme that makes a ssDNA copy from an RNA template.

  2. Thinking about the question "Should "txn, RNA-dependent", e.g. reverse txn be uder "gene expression", I talked to my coworker Julie, who is more knowledgable about viruses than I am, and we weren't sure that "reverse txn" could be classified as always "gene expression" or as always "RNA-dependent DNA replication"; it seems that reverse txn is used in both contexts. In addition, once you start considering viral life cycles, is it always true that "txn, DNA-dependent" is part of "gene expression" or are there viruses that use DNA intermediates in the process of making an RNA genome?

Original comment by: mah11

gocentral commented 15 years ago

one more from email:

== Midori, 2 Dec 2008 12:34:04 +0000 (GMT) == Thanks for all the thoughts so far. Comments on Karen's comments inline ...

On Mon, 1 Dec 2008, Karen Christie wrote:

> Hmmm, a tricky question... > > Reading through the whole thread so far, I have several comments. > > 1. Based on the current defs of "RNA-dependent DNA replication" > (which includes the phrase 'RNA-dependent DNA polymerases > (e.g. reverse transcriptase)' and of "transcription, RNA-dependent" > which has 'reverse transcriptase' as a synonym, these two terms do > seem to be identical. > > However, it seems to me that the reverse transcription (txn) step is > only half of "RNA-dependent DNA replication" because reverse txn > only makes a ssDNA copy. This ssDNA then serves as the template for > production of dsDNA (going off my old biology book). So, perhaps the > def of "RNA-dependent DNA replication" needs to be broader to > encompass the whole process, and "transcription, RNA-dependent" > could have a part_of relationship to such a redefined/new term.

That's an interesting point, and one that hadn't occurred to me, since I was going by just the existing GO defs. Your proposed changes sound like they would work well, assuming that reverse transcription always happens in the context of dsDNA synthesis (I don't know of any non-experimental exceptions). Perhaps the broader process should be named RNA-dependent DNA synthesis or something to that effect, rather than use 'DNA replication' -- DNA replication seems a bit odd for a process that doesn't start with DNA.

> 2. Harold's example of "A negative-sense ssRNA virus genome is
> copied by an RNA polymerase to form positive-sense RNA" is currently > outside the scope of the question at hand, since this is not > included in either form of transcription represented in GO by > current defs: > - txn, RNA-dependent = ssDNA copy from RNA template > - txn, DNA-dependent = ssRNA copy from DNA template > > I'm definitely not an expert on all the ways viruses can do things, > so it may be that we need to represent making a ssRNA copy from an > RNA template, but this is currently not included in the def of "txn,
> RNA-dependent".

I think we'll need a new child of RNA biosynthetic process for this. Also mRNA transcription has mRNA biosythesis, mRNA biosynthetic process and mRNA synthesis as broad synonyms. Although the 'broad' scope is correct, we probably ought to remove those synonyms and create a new term instead. Even if we don't, the viral processes as in Harold's example are still making RNA from RNA, and therefore are not transcription. (The rRNA and tRNA terms also have corresponding synonyms, but I don't know of any viruses that encode rRNA or tRNA ...)

> 3. While I see where Harold is going in the idea that it's "all in
> what the copy is used for", I'm not sure that we can use this to > distinguish. In terms of how enzymologists think of reverse > transcriptase, it's the enzyme that makes a ssDNA copy from an RNA > template.

I agree with Karen here -- we can't use "what the copy is used for" to determine whether a given process is transcription. It doesn't make any sense for GO to abandon the definition of transcription that the molecular biology community has long established; it's poor ontological practice to define a process in terms of events that happen after the process itself has ended; and there would be immense (and absurd) practical problems as well. For example, what if an mRNA is synthesized, but then degraded before it's translated into protein? Does that mean that the process by which it was synthesized wasn't transcription after all?

> 4. Thinking about the question "Should "txn, RNA-dependent",
> e.g. reverse txn be uder "gene expression", I talked to my coworker
> Julie, who is more knowledgable about viruses than I am, and we
> weren't sure that "reverse txn" could be classified as always "gene > expression" or as always "RNA-dependent DNA replication"; it seems
> that reverse txn is used in both contexts. In addition, once you
> start considering viral life cycles, is it always true that "txn, > DNA-dependent" is part of "gene expression" or are there viruses
> that use DNA intermediates in the process of making an RNA genome?

In a sense, all retroviruses do this -- the dsDNA produced by reverse
transcription + second strand synthesis can be integrated into the
host genome, where host transcription machinery synthesizes RNA
molecules that are effectively new copies of the viral RNA genome.

So I think we've convinced ourselves that the generic 'transcription'
term should not remain part of gene expression. I'm pretty confident
that we can put DNA-dependent transcription down as part of gene
expression instead.

m

Original comment by: mah11

gocentral commented 15 years ago

Just a little reminder. If we move txn out from under gene expression, we also need to move the regulation of txn terms from regulation of gene expression.

Original comment by: tberardini

gocentral commented 15 years ago

More of the thread transcribed (also not in the mol biol sense!) from email exchange (read down):

== Alex, Tue, 02 Dec 2008 21:16:03 -0500

In viruses, such as Corona and Toga viruses, (+)-strand subgenomic RNAs that act as mRNA are made from a negative stranded genomic RNA template. Virologists refer to this process as "transcription" in hundreds of papers, a usage which dates back over 30 years (PMID:173940). This not RNA replication, but a different process (using many of the same enzymes to be sure) under a different type of regulation.

== Karen, Tue, 2 Dec 2008 15:33:46 -0800 (PST)

I've sent an email to my old advisor to see if she has thoughts on this issue.

== Midori, Wed, 3 Dec 2008 10:11:46 +0000 (GMT)

Thanks. Considering everything from this email thread, I think we really need input from outside our little GO circle.

p.s. It also sounds as though "transcription" has been used with more than one meaning, so GO may end up not having a term named simply "transcription", but instead keeping only terms with more specific names.

== Harold, Wed, 03 Dec 2008 09:38:45 -0500

That's why I think I like the concepts of a DNA transcripiton and an RNA transcripiton, both of which yield a transcript.

== Alex, Wed, 03 Dec 2008 09:47:21 -0500

Perhaps it is better to be completely clear in either the term name or in an exact synonym:

DNA transcription = RNA transcription from a DNA template RNA transcription = RNA transcription from an RNA template reverse transcription = DNA transcription from an RNA template

== Harold, Wed, 03 Dec 2008 09:49:45 -0500

The fact that term has been used in a different scope from which it was originally intended means that there is extreme ambiguity in it's use, which is sloppy.

We need to ask

  1. what IS transcription; who coined the term and in what circumstances.
  2. more related to Midori's 1rst question: is the reverse of the process a type of the process; I would say no in any case I can think of. So, reverse transcription is not a type of transcription, no matter what we decide IS "transcription.

and, choking on the dust I'm bushing off from a box in my attic, from a textbooks over 30 years old" Transcription is the process by which information contained in DNA is copied, by base paring, to form a complementary sequence of ribonucleotides, a RNA chain.."and similar scattered references in a 1966 Cold Spring Harbor Symposium volume (XXXI).

But I would still be comfortable distinguishing DNA based transcription from RNA based transcription

== Alex, Wed, 03 Dec 2008 10:16:48 -0500

We represent the language of biologists. Usage changes over the years. Just because the original meaning of the word has expanded does not mean other usages are necessarily wrong or sloppy. Furthermore, we have long accepted that different communities of biologists use the same word in different ways. It is up to us create the appropriate terms and write term names and definitions that reflect the different usages we see in the whole of biology. It is not for us to decide that an accepted usage of transcription in the phrase "reverse transcription" cannot be represented in the GO -- it should, perhaps as a term name, perhaps an an exact synonym.

Furthermore, in 1966, reverse transcription had not even been discovered, and was probably considered impossible by biologists of the time, so no definition would contain a reference to it.

To me, transcription simply means the synthesis of a strand of nucleic acid of a template strand of nucleic acid. Types of transcription include:

  1. transcription of mRNA from an DNA template
  2. transcription of mRNA from an RNA template
  3. transcription of DNA from an RNA template
  4. transcription of DNA from a DNA template (!)

Furthermore transcription is part of the process of

  1. genomic RNA replication in RNA viruses
  2. DNA replication

and probably some other processes as well.

(please don't fall out of your chair!)

== Harold, Wed, 03 Dec 2008 10:27:28 -0500

Alexander Diehl wrote: > > Furthermore, in 1966, reverse transcription had not even been discovered, and was probably > considered impossible by biologists of the time, so no definition would contain a > reference to it. But a reverse of a process is still not and instance or part of a process I would think.

> To me, transcription simply means the synthesis of a strand of nucleic acid of a template > strand of nucleic acid. Types of transcription include: > > 1. transcription of mRNA from an DNA template agree > 2. transcription of mRNA from an RNA template agree > 3. transcription of DNA from an RNA template agree > 4. transcription of DNA from a DNA template (!) > Alex, can you give me an instance where #4 above is/was used?

What transcription is a part of is not the question at the moment (certainly creation of the RNA primer for DNA synthesis is part of some DNA replication). I still contend that the use of "transcription" is at least confined to a process of making RNA molecule

> (please don't fall out of your chair!) > I don't have enough room in my cubicle to do that 8-)

== Alex, Wed, 03 Dec 2008 10:54:41 -0500

Harold,

I don't know of an example of 4 to cite -- it simply follows from the idea of transcription being "the synthesis of a strand of nucleic acid of a template strand of nucleic acid." We can obviously by fiat in the GO state that synthesis of DNA from a DNA template is not a type of transcription, since this particular usage is not supported by the literature.

But "reverse transcription" is a named biological process in the literature, and we must represent it in the GO with the string "reverse transcription" either as a term name or synonym. Whether we can agree upon a broad-enough definition of transcription to accommodate this term as a child is the question. In any case whatever we choose "transcription" to be in the GO it must cover at a minimum #1 and #2 of my list, lest we ignore 30+ years of virology, and using my suggested definition of transcription allows it to accommodate #3 as well.

== Harold, Wed, 03 Dec 2008 11:00:43 -0500

Oops, Actually I meant to question #3.

== Karen, Wed, 3 Dec 2008 09:37:56 -0800 (PST)

I don't think we (we being a subset of GOC editors) can arbitrarily decide that transcription is restricted to making an RNA molecule. I agree with Alex that we need to reflect the current usage of the research community (and that textbooks and the Oxford Dictionary that we used for many defs are not good sources for getting a comprehensive view of usage of a word).

Perhaps transcription is making a single stranded copy of nucleic acid, or perhaps as Midori suggested the possibility, there may not be a cohesive grouping term for these three things that are known to occur:

  1. making RNA copy from DNA template
  2. making RNA copy from RNA template
  3. making DNA copy from RNA template

I think we should do some research and/or get input from the research community before making changes in this area.

== Harold, Wed, 03 Dec 2008 18:24:37 -0500 From: Harold Drabkin <hjd@informatics.jax.org> To: Karen Christie <kchris@genome.stanford.edu> Cc: Ontology Editors <ontology-editors@genome.stanford.edu> Subject: Re: [Ontology-editors] forward and reverse transcription

I don't think there is anything arbitrary about this at all.

The sequence ontology defines a transcript as " An RNA synthesized on a DNA or RNA template by an RNA polymerase."

Shouldn't our use of transcription be consistent with the use of terms in SO. I The making of a transcript is transcription. The templated making of a transcript is transcription;

The term reverse-transcription is the templated syntehesis of DNA from an RNA template. It is fundamentally different. Transcription uses ribonucleotides wherease revere transcription uses deoxyribonucleotides. Reverse transcription is not a type transcription. It is a type of templated DNA synthesis not transcription. The "reverse" is in terms of the central dogma reversal, not the reverse of transcription itself. A true reverse of transcription would be the disassembly of the RNA transcript into ribonucleotide triphosphates, I suppose in the presence DNA.

== Karen, Wed, 3 Dec 2008 15:28:47 -0800 (PST)

and where did SO get there definition? Maybe they just assumed they "knew" what transcription was too. I just think it's worth doing some due diligence to make sure that we understand what the research community thinks is appropriate use of the word "transcription".

Then, we should make both GO and SO reflect that usage so that we are consistent.

== Midori, Thu, 4 Dec 2008 09:19:35 +0000 (GMT)

I agree completely with Karen. We need community input, and if both GO and SO have to change, so be it.

Before Alex chimed in, I was unaware of the virus community's usage, which makes it a no-GO (groan) to use DNA<->RNA conversion as the defining feature of transcription. That's rather unfortunate, but upon further reflection, it occurs to me that it would also look quite odd to count RNA primer synthesis during DNA replication as transcription.

That last point does also argue against defining transcription as any template-based RNA synthesis, though. Maybe we won't be able to have a single term encompassing all transcription and only transcription (regardless of whether the experts regard reverse transcription as transcription).

Original comment by: krchristie

gocentral commented 15 years ago

email correspondance with Caroline Kane

Initial question sent to Caroline Kane (U. California at Berkeley)

The issue that we have been discussing today is whether or not "reverse transcription" is a type of "transcription", or whether it is an entirely different thing. This has led to the question of exactly how one should define "transcription", particularly with respect to whether "transcription" is inclusive of only one, only two, or all three of these processes:

The general textbooks usually say something like "production of mRNA from DNA". However, since such textbooks sometimes oversimplify, I wasn't sure that we should use such a strict definition just based on general textbooks. Basically, we have thought of three possible ways to define transcription:

  1. central dogma based def => only making RNA copies from DNA

  2. making RNA copies, from either DNA or RNA copies. This would include "classic" txn and also making RNA copies from RNA templates, but would exclude reverse transcription

  3. making single strand copies of nucleic acid - the broadest of the three defs, basically trying to come up with a def that is inclusive of reverse transcription on the thought that people would want to see a general "transcription" term be inclusive of "reverse transcription"

== Caroline Kane Thu, 04 Dec 2008 16:00:28 -0800

Hi Karen,

Here are my thoughts on your questions. Also, I suggest that you ask Joan Conaway or Tom Steitz and tell them I sent you.

As for me, reverse transcription got its name because transcription is usually DNA to RNA. So it seemed logical to Baltimore et al, that RNA to DNA be reverse transcription. RNA to RNA is not considered transcription unless it is in the synthesis of a mRNA or some RNA that has a function (miRNA, tRNA, etc)....my virus friends have browbeaten me into that one. However, I am told, positive stranded RNA viruses never undergo transcription...they undergo replication, even when they are remaking the positive strand.

As you know, I am anal compulsive about the use of words in science because the words can lead to confusion when used without precision. The word transcription conjures up mechanistic impressions about how anything called transcription works...and working like DNA to RNA is what is conjured even though RVTase are really DNA polymerases with low processivity, higher error rates, different regulation than DNA dependent RNA polymerases.

These thoughts may just add fuel to the confusion fire, but I hope not. You can avoid the whole thing by saying nucleic acid synthesis and indicate which type of synthesis. BUT, in GO, I know there are all the trees for transcriptional regulation and such (most of which have seemed to me to be DNA sequence specific binding proteins). So, if SGD can lead to clarification, you would do the entire scientific community a large service.

If you want, when you contact Joan and Tom, you can send them these comments to see if they agree or disagree. Tom has done structures of all kinds of nucleic acid synthesizing proteins, so I suspect he will have especially strong opinions...and those are the most fun!!

Best,

Caroline

== Karen, Fri, 5 Dec 2008 10:38:32 -0800 (PST)

Hi Caroline,

Thanks so much for taking the time to think about this and to suggest others to also ask for their opinions.

Before I send emails to others, I'd just like to confirm that I understood your preference. It seems to me that you think that the three things I mentioned:

are basically different from each other, that despite the use of the same word "transcription", that "classic" transcription (DNA to RNA) and reverse transcription are not really similar. And then RNA to RNA is generally not considered to be transcription either (with the annoying caveat of unless the resulting RNA has a function).

> From this, it might be clearer in the ontology to just do something like what I have below, where the parenthetical expressions would be included as synonyms.

- nucleic acid synthesis -- DNA synthesis --- DNA synthesis from RNA template (reverse transcription) -- RNA synthesis --- RNA synthesis from DNA template (transcription) --- RNA synthesis from RNA template (RNA replication)

-Karen

== Caroline, Fri, 05 Dec 2008 11:48:01 -0800

HI Karen,

Those are indeed my thinking...and I like the ontology suggestion.

Caroline

Original comment by: krchristie

gocentral commented 15 years ago

Karen, thanks for following this up with Caroline. It will also be valuable to hear from the others.

I find myself wishing I had a time machine so I could go back and tell the virus community "get your usage sorted out NOW", but oh well. I'd be happy to use the ontology sketch you proposed as a starting point.

m

Original comment by: mah11

gocentral commented 15 years ago

Gosh I thought that was going to be an easy one, but what a can of worms. Thanks Harold for all the imagery of falling off chairs and searching in attics! val

Original comment by: ValWood

gocentral commented 15 years ago

Hi,

I'll send emails to the 2 other people Caroline suggested tomorrow. Friday, I did some poking around in PubMed to better understand viral "transcription" vs replication. I learned enough to feel that I need to better understand that a bit better before we fiddle with the ontology. However, I did find a couple quotes, one on the reverse transcriptase enzyme and a second on the use of the word "transcription" in the context of RNA->RNA copying, that I'll include here now.

I'll also say now that Eurie felt strongly that we need to keep the word "transcription" in the main term name for "classic" transcription, i.e. DNA->RNA, so maybe that term would be called something like "transcription from DNA" with "RNA synthesis from DNA template" as a synonym.

-Karen

relevant quotes:


Schultz SJ, Champoux JJ. RNase H activity: structure, specificity, and function in reverse transcription.Virus Res. 2008 Jun;134(1-2):86-103. Epub 2008 Feb 7. PMID: 18261820

QUOTE: Reverse transcription is performed by the retroviral enzyme called reverse transcriptase. This multifunctional enzyme carries out RNA-dependent DNA polymerization, DNA-dependent DNA polymerization, strand displacement synthesis, strand transfers, and degrades the RNA strand in RNA/DNA hybrids. To perform these diverse functions, reverse transcriptase uniquely combines two distinct enzymatic activities, a DNA polymerase activity that uses RNA or DNA as a template, and an RNase H activity that cleaves the RNA strand of an RNA/DNA hybrid (Gilboa et al., 1979).


Pasternak AO, Spaan WJ, Snijder EJ. Nidovirus transcription: how to make sense...? J Gen Virol. 2006 Jun;87(Pt 6):1403-21. Review. PMID: 16690906

QUOTE: *When its definition is followed to the letter, the term 'transcription' (i.e. 'the process by which genetic information encoded in one strand of DNA is copied into a complementary RNA strand') does not apply to the synthesis of sg mRNAs by nidoviruses and other RNA viruses. Nevertheless, there is a clear functional parallel (production of RNA templates for protein synthesis) and the term 'transcription' has been used in studies on coronavirus sg mRNA synthesis from the very start. Consequently, for the purpose of this review and regardless of the lack of a DNA template, we will use the term 'transcription' for the synthesis of sg plus strands (sg mRNAs). Genome amplification, which results in the production of a full-length mRNA, will be referred to as 'replication'.

Original comment by: krchristie

gocentral commented 15 years ago

update on progress from Karen, 12-9-2008

I emailed Joan Conaway and Tom Steitz yesterday. The ontology structure I included in the email to them has evolved a little bit from the one I sent to Caroline, mostly due to slightly increased understanding of various viral processes. Please note though that I do not yet feel that I understand viruses well enough to be confident that the proposal below represents viral biology adequately. Consider this a working model still in progress.

- nucleic acid synthesis -- DNA synthesis --- DNA synthesis from RNA template (reverse transcription) -- RNA synthesis --- transcription from DNA (RNA synthesis from DNA template) --- RNA synthesis from RNA template (RNA replication) ---- synthesis of ssRNA from dsRNA template (transcription from dsRNA; plus-strand synthesis) ---- synthesis of dsRNA from ssRNA template (RNA replication; minus-strand synthesis)

Here is the response from Joan Conaway:

Date: Tue, 9 Dec 2008 10:56:00 -0600 From: "Conaway, Joan" at the Stowers Institute for Medical Research in Kansas City, MO Subject: RE: defining "transcription" vs "reverse transcription"

Hi Karen, In general I agree with Caroline and think your proposed diagram nicely focuses on functional relationships without getting hung-up on definitions. I think of transcription as being any DNA-directed RNA synthesis, not limited to synthesis of mRNAs. I agree that reverse transcription (RNA to DNA) wouldn't be considered transcription, but I'm not sure that one would never consider RNA-directed RNA synthesis transcription. I'm not sure who would be best from the virology community to provide more insight. Someone who is an outstanding nucleic acid enzymologist who might be able to give you better insights and/or suggest some other(s) to contact would be Bob Lehman in the Biochemistry department at Stanford. I suspect he will have a particularly good perspective. Best wishes, Joan

Original comment by: krchristie

gocentral commented 15 years ago

Karen,

Many types of RNA viruses transcribe mRNA from single-stranded RNA templates, for instance alphaviruses like Sindbis virus and Semliki Forest virus. PMID:7968923 provides a fairly long-winded review of this and other aspects of the biology of these viruses. Basically promoter elements within a full-length single-stranded, negative-stranded RNA genomic copy (the genomic RNA is a positive-stranded ssRNA packaged in the virion) act to bind RNA-RNA polymerases that then transcribe a 26S subgenomic RNA that serves as an mRNA for the synthesis of the viral structural proteins. This system has been worked on for decades and again, production of the mRNA here has been consistently described as "transcription." The use of the word transcription is entirely appropriate, as it is not the genomic RNA that is being replicated but rather an mRNA that is being produced. Thus we absolutely need to use the word transcription as part of the term name or an exact synonym.

Replication of these viruses and many others involves synthesis of ssRNA from ssRNA templates, using a negative-strand ssRNA intermediate. You really need to have separate terms for the transcription of the subgenomic mRNA and the replication of the full-length genomic RNA.

Thanks,

Alex

Original comment by: addiehl

gocentral commented 15 years ago

Perhaps a useful definition of transcription might be, "The synthesis of any subgenomic-length RNA from a DNA or RNA template."

-- Alex

Original comment by: addiehl

gocentral commented 15 years ago

Alex - that sounds like a good start, but I think we need to exclude primer synthesis during DNA replication, and preferably by some more graceful means than just tacking "except primer synthesis" onto the def.

m

Original comment by: mah11

gocentral commented 15 years ago

I have sent off an email to David Baltimore to see if he has any thoughts on this.

Original comment by: hdrabkin

gocentral commented 14 years ago

Any outcome for this one? Val

Original comment by: ValWood

gocentral commented 14 years ago

I haven't heard anything for quite a while ...

Original comment by: mah11

gocentral commented 14 years ago

. "reverse transcription" is a term that was never meant to imply that it was a type of transcription, but was a term to describe the use of an RNA template to make DNA. Ask yourself: What is being synthesized: DNA; therefore "reverse transcription" is a form of DNA synthesis. Think of the synthesis of two types of nucleic acd DNA synthesis RNA synthesis

Which of the above does the term describe.

I really hate it that the Oxford dictionary of BC and MB has included both under transcription.

Original comment by: hdrabkin

gocentral commented 14 years ago

Yeah, it's causing a heap o' trouble. What we haven't managed to accomplish yet is figuring out how we should define transcription. I wish we could just make 'transcription' (GO:0006350) obsolete, but there are too many annotations directly to it. I bet every blasted one of the annotations could be moved -- there must be enough information to choose between "forward" transcription, reverse transcription, viral-style transcription, etc. But the numbers are just daunting ... thousands of gps ... argh.

Maybe we should just go with Alex's suggestion from 2008-12-09 19:57 and hide primer synthesis under the rug ... <sigh>

m

Original comment by: mah11

gocentral commented 14 years ago

If its is incorrect maybe we should bite the bullet and fix it as it will need to be done eventually.

There only appear to be about 400 manual direct mappings? that isn't too many distributed between all of the participaring databases. ...and really it means that the curators have not selected a specific enough term so its bad annotation practice to leave these annotations here.

There may be a lot of IEA mappings but if Emily and Interpro were given advance notice to fix these (say a few months) before the obsoletion went ahead then there would not be a big "annotation gap".

In the meantime a commnet telling a curator that they probably want to use a more specific term would help to stop more annotations accumulating.

val

Original comment by: ValWood

gocentral commented 14 years ago

OK, over lunch Val and I hatched another idea: based on the notion that when people* say "transcription" they almost always mean "forward" transcription, aka "transcription, DNA-dependent" (GO:0006351; def: "The synthesis of RNA on a template of DNA"), could we merge the parent (GO:0006350) into GO:0006351? If we're having this much trouble coming up with a definition for a grouping term, perhaps that really means that the grouping is artificial, and we should stop trying to force it. We would just keep (or add) terms for the three phenomena we've been discussing, with suitable DNA metabolism and/or RNA metabolism parents, and any child terms we need:

- making RNA copies from DNA ("classic" transcription)

We suspect that most, probably all, annotations would still be correct.

thoughts? m

*at least people who don't work on viruses; we doubt that GO:0006350 has been used for viral gps, though

Original comment by: mah11

gocentral commented 13 years ago

This has, at long last, been superseded by proposals that form part of the major transcription overhaul:

http://wiki.geneontology.org/index.php/Proposal\_for\_fate\_of\_%22transcription%22\_and\_corresponding\_regulation\_terms http://wiki.geneontology.org/index.php/Proposal\_for\_obsoleting\_%22transcription,\_RNA\_dependent%22

Original comment by: mah11

gocentral commented 13 years ago

Original comment by: mah11

gocentral commented 12 years ago

Original comment by: mah11