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Many RNAi-related term/structure changes; new ciliate terms #2040

Closed gocentral closed 9 years ago

gocentral commented 19 years ago

Hi,

This is Nick Stover from the Tetrahymena Genome DB again. We need to request one more set of terms for an active area of ciliate research.

A process related to RNA interference (RNAi) is used by the ciliate Tetrahymena to direct the excision of parts of its genome. In order to accommodate this aspect of ciliate biology, and to represent the commonalities known and expected among this and other RNAi-related processes, Im requesting the following changes to the ontology. If you would like to view a diagram of the existing relationships (only the affected/relevant terms) compared with these proposed changes, please visit: http://genetics.stanford.edu/~nick/pictures/RNAiGOTree.jpg and http://genetics.stanford.edu/~nick/pictures/ RNAiGOTreeProposed.jpg Review articles on this process and its relationship to others involving small RNAs can be found in PMID: 15196465 and PMID:

  1. Other terms are defined at: http://genetics.stanford.edu/~nick/progdnaelim.shtml

Additions

name: programmed_DNA_elimination namespace: process def: Removal of micronuclear-limited sequences, internal eliminated sequences (IES) and breakage eliminated sequences (BES), from the developing macronucleus (anlage) of a ciliate. relationship: is_a GO:0006139 : nucleobase, nucleoside, nucleotide and nucleic acid metabolism

name: scnRNA production namespace: process def: Cleavage of noncoding, double-stranded RNAs transcribed from the micronuclear genome to produce scnRNAs, small RNAs (~28 nucleotides) that direct the deletion of micronuclear-limited sequences from the developing macronuclear genome. relationship: part_of PROPOSED: Programmed DNA Elimination; is_a PROPOSED: dsRNA fragmentation

name: Chromosome Breakage namespace: process def: Regulated cleavage of the developing macronuclear genome at a limited number of chromosome breakage sites (CBS). The macronuclear destined segment (MDS) sequence adjacent to the CBS (or separated from it by a BES) receives a macronuclear telomere following chromosome breakage. relationship: part_of PROPOSED: Programmed DNA Elimination -- Im not sure if this should be a Sensu Ciliophora term, given the generic name of the process

name: dsRNA Fragmentation namespace: process def: Cleavage of double-stranded RNA molecules by an RNaseIII- family enzyme to produce small RNAs (generally 20-30 nucleotides, depending on species) with biological function. relationship: is_a GO:0006396 : RNA processing

name: Small RNA-Mediated Chromatin Silencing namespace: process def: Repression of transcription by conversion of large regions of DNA into heterochromatin, directed by small RNAs sharing sequence identity to the repressed region." relationship: is_a GO:0006342 : chromatin silencing

Obsoletions

GO:0010194 : microRNA metabolism ( 1 gene annotated ) GO:0010195 : microRNA biosynthesis ( 1 gene annotated ) GO:0030918 : microRNA processing ( 0 genes annotated )

The definition and parentage of the term microRNA biosynthesis implies the assembly of microRNAs from either nucleotides or short (smaller than the miRNAs) RNA fragments, which is not suggested in the cited abstract (TAIR accession Publication: 501707121). The absence of small RNAs noted in this abstract is likely due instead to the inability to fragment larger precursor RNAs.

miRNA production from a primary transcript is known at the moment to include two steps: an initial cleavage of the primary RNA transcript to ~70 nt RNAs, then a second step to create the functional miRNAs (PMID: 15211354). I am unaware of intermediate steps in the production of siRNAs or scnRNAs. As the definition for GO:0035196:miRNA-mediated gene silencing, production of miRNAs is written, both steps are covered. The definition of this term is broad enough to allow this term to be used as a synonym for the three obsoleted microRNA terms.

id: GO:0010194 name: microRNA metabolism namespace: process def: "The chemical reactions and physical changes involving microRNA, a large family of 21-22 nucleotide non-coding RNAs with presumed post-transcriptional regulatory activity." [TAIR:sm] exact_synonym: "miRNA metabolism" [] is_a: GO:0016070

id: GO:0010195 name: microRNA biosynthesis namespace: process def: "The formation from simpler components of microRNA, a large family of 21-22 nucleotide non-coding RNAs with presumed post-transcriptional regulatory activity." [TAIR:sm] exact_synonym: "miRNA biosynthesis" [] is_a: GO:0009058 is_a: GO:0010194

id: GO:0030918 name: microRNA processing namespace: process def: "Any process involved in the conversion of a primary microRNA transcript into a mature microRNA molecule." [GO:mah ""] exact_synonym: "miRNA processing" [] is_a: GO:0006396 is_a: GO:0010194

id: GO:0035196 name: miRNA-mediated gene silencing, production of miRNAs namespace: process def: "Cleavage of stem-loop RNA precursors (pre-miRNAs) that are encoded within plant and animal genomes into microRNAs (miRNAs), a class of small RNAs that primarily silence genes by blocking the translation of mRNA transcripts into protein." [PMID:15066283, PMID:15066275] exact_synonym: "microRNA-mediated gene silencing, production of microRNAs" [] is_a: GO:0010195 relationship: part_of GO:0035195

Altered Relationships:

Currently GO:0035196:miRNA-mediated gene silencing, production of miRNAs is a child term of GO:0010195:microRNA biosynthesis (to be obsoleted). I propose that it should be a child of PROPOSED: dsRNA fragmentation, along with GO:0030422:RNA interference, production of guide RNAs and PROPOSED: scnRNA production.

id: GO:0030422 name: RNA interference, production of guide RNAs namespace: process def: "Cleavage of double-stranded RNA to form small interfering RNA molecules (siRNAs) of 21-23 nucleotides." [PMID:11524674] is_a: GO:0016070 relationship: part_of GO:0016246

Definitions of other terms in the diagrams:

id: GO:0030423 name: RNA interference, targeting of mRNA for destruction namespace: process def: "The process by which small interfering RNAs target cognate mRNA molecules for degradation." [PMID:11524674] relationship: part_of GO:0016246

id: GO:0016246 name: RNA interference namespace: process Synonyms: RNAi def: The process by which double-stranded RNAs silence cognate genes.

id: GO:0035194 name: RNA-mediated gene silencing namespace: process def: "Gene inactivation (silencing) triggered by small RNAs." [PMID:15066283, PMID:15066275] is_a: GO:0016441

id: GO:0035195 name: miRNA-mediated gene silencing namespace: process def: "Down regulation of gene expression through the action of microRNAs (miRNAs). miRNAs are endogenous 21-24 nucleotide small RNAs processed from stem-loop RNA precursors (pre-miRNAs). They act as guides for the miRNA-induced silencing complex (miRISC) and primarily silence genes by blocking the translation of mRNA transcripts into protein." [PMID:15066283, PMID:15066275] exact_synonym: "microRNA-mediated gene silencing" [] is_a: GO:0035194

id: GO:0035197 name: siRNA binding namespace: function def: "Interacting selectively with a small interfering RNA, a 21-23 nucleotide RNA that is processed from double stranded RNA (dsRNA) by an RNAse enzyme." [PMID:15066283, PMID:15066275] exact_synonym: "small interfering RNA binding" [] is_a: GO:0003723

id: GO:0035198 name: miRNA binding namespace: function def: "Interacting selectively with a microRNA, a 21-23 nucleotide RNA that is processed from a stem-loop RNA precursor (pre-miRNA) that is encoded within plant and animal genomes." [PMID:15066283] exact_synonym: "microRNA binding" [] is_a: GO:0003723

id: GO:0006342 name: chromatin silencing alt_id: GO:0016440 namespace: process def: "Repression of transcription by conversion of large regions of DNA into an inaccessible state often called heterochromatin." [PMID:10219245] comment: Note that this process is the opposite of chromatin- mediated maintenance of transcription. This regulation is exemplified by members of the Polycomb group, which maintain the inactive state of homeotic gene transcription. synonym: "TGS" [] synonym: "heterochromatin formation" [] synonym: "transcriptional gene silencing" [] exact_synonym: "chromatin-mediated maintenance of transcriptional inactivation" [] exact_synonym: "chromatin-mediated silencing" [] is_a: GO:0006338 is_a: GO:0016458 is_a: GO:0045814 is_a: GO:0045892

id: GO:0016441 name: posttranscriptional gene silencing namespace: process def: "Posttranscriptional gene inactivation ('silencing') both of transgenes or dsRNA introduced into a germline, and of the host gene(s) homologous to the transgenes or dsRNA. This silencing is triggered by the introduction of transgenes or double-stranded RNA (dsRNA), and occurs through a specific decrease in the level of mRNA of both host genes and transgenes." [WB:ems, PMID:11713190] synonym: "quelling" [] exact_synonym: "PTGS" [] is_a: GO:0016458 is_a: GO:0040029 related_synonym: "cosuppression" []

id: GO:0035087 name: RNA interference, siRNA loading onto RISC namespace: process def: "The transfer of small interfering RNA molecules (siRNAs) from the Dicer family of enzymes that cleave the double-stranded RNA, onto the nuclease-containing RNA-initiated silencing complex (RISC)." [PMID:14512631, FB:bf] relationship: part_of GO:0016246

Reported by: nastover

Original Ticket: "geneontology/ontology-requests/2047":https://sourceforge.net/p/geneontology/ontology-requests/2047

gocentral commented 19 years ago

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> name: Chromosome Breakage > -- I'm not sure if this should be a 'sensu Ciliophora' > term, given the generic name of the process

In most, maybe all, other contexts, chromosome breakage is not a normal, regulated occurrence. If no other organisms have any normal chromosome breakage processes, the term does not have to be 'sensu Ciliophora'; we can use a comment to point out that the term is not to be used for DNA damage or other abnormal situations.

> Obsoletions

This sounds reasonable. Could you suggest comments for the obsolete terms (see http://www.geneontology.org/GO.format.html\#comments)?

I'm a little confused by this passage: 'The definition of [GO:0035196] is broad enough to allow this term to be used as a synonym for the three obsoleted microRNA terms.'

Does this imply that GO:0010494, GO:0010495, and GO:0030198 should be merged with GO:0035196 rather than obsoleted? Or should the text strings be used as synonyms, or should the comments on the obsolete terms simply direct one to GO:0035196 (the last option would be fine, possibly the best).

Apart from these small things, this proposal looks fine. Do you plan to implement it yourself, or would you like us to do so?

midori

Original comment by: mah11

gocentral commented 19 years ago

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>> Obsoletions > >This sounds reasonable. Could you suggest comments for >the obsolete terms (see >http://www.geneontology.org/GO.format.html\#comments)?

Ill certainly try:

term: microRNA biosynthesis goid: GO: 0010195 comment: This term was made obsolete because it represents a process that is not known to occur. To update annotations, use the biological process term 'miRNA-mediated gene silencing, production of miRNAs; GO:0035196.'

term: microRNA metabolism goid: GO:0010194 comment: This term was made obsolete because it implies further processing of an end product rather than its production. To update annotations, use the biological process term 'miRNA-mediated gene silencing, production of miRNAs; GO:0035196.' --am I right about this? When I think of the process glucose metabolism, for example, I dont think of the breakdown of glycogen into glucose as part of that process. Same thoughts apply here.

The third term is trickier. The original definition was:

id: GO:0030918 name: microRNA processing namespace: process def: "Any process involved in the conversion of a primary microRNA transcript into a mature microRNA molecule." [GO:mah ""] exact_synonym: "miRNA processing" [] is_a: GO:0006396 is_a: GO:0010194

My first inclination was to obsolete this term for essentially the same reason stated above for microRNA metabolism, assuming all three terms were intended to be synonymous with miRNA-mediated gene silencing, production of miRNAs. However the definition given for microRNA processing is less vague and hits on a good point, so please allow me to rethink that here.

First a more in depth description miRNA biogenesis (from PMID: 15211354): A section of the genome gets transcribed (into a pri-microRNA [or, primary microRNA]), which folds over on itself to created double- stranded RNA. These long transcripts get cleaved first into ~70 bp fragments (called pre-microRNA), then into ~22 bp fragments. The ~22 bp fragments are called microRNAs, and inhibit genes with which they share identity.

It appears to me that capturing the processing of pri-microRNA transcripts into the larger ~70 bp fragments was part of the intent of id: GO:0030918. This is still a valuable term, as at least one gene mentioned in the review above is specific to this early step. However, if this term is kept I would suggest both changing the term name and including an equivalent term to describe the second step of miRNA production (cleavage of the ~70 bp pre-miRNAs to ~22 bp).

In that case:

(altered) id: GO:0030918 name: primary_microRNA_processing namespace: process def: "Any process involved in the conversion of a primary microRNA (pri-microRNA) transcript into a pre-microRNA molecule." exact_synonym: "pri-miRNA processing" [] part_of: GO:0035196

(new) id: GO:PROPOSED name: pre-microRNA_processing namespace: process def: "Any process involved in the conversion of a pre-microRNA molecule into a mature microRNA molecule." exact_synonym: "pre-miRNA processing" [] part_of: GO:0035196

and to clear up the grouping term: (altered) id: GO:0035196 name: miRNA-mediated gene silencing, production of miRNAs namespace: process def: "Cleavage of double-stranded RNA precursors into microRNAs (miRNAs), a class of small RNAs that primarily silence genes by blocking the translation of mRNA transcripts into protein." [PMID:15066283, PMID:15066275] exact_synonym: "microRNA-mediated gene silencing, production of microRNAs" [] is_a: GO:PROPOSED: dsRNA fragmentation relationship: part_of GO:0035195

If this seems like too much detail the term could be obsoleted with

term: microRNA processing goid: GO: 0030918 comment: This term was made obsolete because it was determined to be synonymous with id: GO:0035196. To update annotations, use the biological process term ' miRNA-mediated gene silencing, production of miRNAs; GO:0035196.'

>I'm a little confused by this passage: 'The definition >of [GO:0035196] is broad enough to allow this term to be >used as a synonym for the three obsoleted microRNA terms.' > >Does this imply that GO:0010494, GO:0010495, and >GO:0030198 should be merged with GO:0035196 rather >than obsoleted? Or should the text strings be used as >synonyms, or should the comments on the obsolete terms >simply direct one to GO:0035196 (the last option would be >fine, possibly the best).

I hope the comments I wrote and the above discussion are clear enough to show why the three obsoletions are a little tricky. If Ive dealt with these terms inappropriately, please let me know.

>Apart from these small things, this proposal looks fine. >Do you plan to implement it yourself, or would you like >us to do so?

Let me see what my fellows at SGD think would be appropriate, and Ill let you know soon.

Thanks, Nick

Original comment by: nastover

gocentral commented 19 years ago

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Thanks for the additional information!

The arguments for making 'microRNA biosynnthesis' and 'microRNA metabolism' obsolete make sense, so I won't dwell on them further.

As for 'microRNA processing' (GO:0030918, it seems to have been intended to cover any/all miRNA processing events, and would make sense as a parent for both steps. If that interpretation makes it redundant with GO:0035196, the two should be merged rather than making GO:0030918 obsolete. I don't think GO:0030918 is intended to represent only the first miRNA processing step. (I added it; this is what I recall thinking at the time, and it still seems to make sense now ...)

So we could have: id: GO:0035196 name: miRNA-mediated gene silencing, production of miRNAs alt_id: GO:00030918 exact_synonym: microRNA processing [some tags not shown]

and two new child terms, one for processing of pri-microRNA transcripts into the larger ~70 bp pre-miRNA fragments and one for cleavage of the ~70 bp pre-miRNAs to ~22 bp miRNA.

Would that work? And if so, what would you like to use as term names for the new child terms?

m

Original comment by: mah11

gocentral commented 19 years ago

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Making those terms synonymous is a fine approach. I like the structure that's come out of this too, since it allows us to add terms specific to siRNA, miRNA, and scnRNA processes without disturbing the others.

Will these work for definitions?

id: PROPOSED name: primary microRNA processing namespace: process def: "Any process involved in the conversion of a primary microRNA transcript into a pre-microRNA molecule." relationship: part_of GO:0035196

id: PROPOSED name: pre-microRNA processing namespace: process def: "Any process involved in the conversion of a pre-microRNA transcript into a mature microRNA molecule." relationship: part_of GO:0035196

The use of both "primary" and "pri-", and "microRNA" and "miRNA" in the literature could necessitate a fair number of synonyms for these terms.
I don't know how detailed GO would like to be regarding this.

Nick

Original comment by: nastover

gocentral commented 19 years ago

Original comment by: mah11

gocentral commented 19 years ago

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One more note: definition references from Nick -

cnRNA production: PMID: 15196465 all the microRNA terms: PMID: 15211354

I think dbxref TGD:ns is probably appropriate for the rest of the new terms, including the component terms.

Original comment by: mah11

gocentral commented 19 years ago

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This is done! changes made as described in the discussion below. The new terms are:

GO:0031047 RNA-mediated gene silencing GO:0031048 small RNA-mediated chromatin silencing GO:0031049 programmed DNA elimination GO:0031050 dsRNA fragmentation GO:0031051 scnRNA production GO:0031052 chromosome breakage GO:0031053 primary microRNA processing GO:0031054 pre-microRNA processing

SF 1058993 may also be of some interest.

cheers, m

Original comment by: mah11

gocentral commented 19 years ago

Original comment by: mah11