position of "intronic snoRNA processing ; GO:0031070"

[gocentral]

Hi,

Was just browsing through and noticed the term "intronic snoRNA processing". Currently, it is a direct child of "snoRNA metabolism" and a sibling of "snoRNA processing". I think it should be an is_a child of "snoRNA processing".

cheers,

-Karen

[Term] id: GO:0031070 name: intronic snoRNA processing namespace: biological_process def: "The biogenesis of a snoRNA molecue which resides within, and is processed from, the intron of a mRNA." [GOC:vw] is_a: GO:0000398 ! nuclear mRNA splicing, via spliceosome is_a: GO:0016074 ! snoRNA metabolism

Reported by: krchristie

Original Ticket: "geneontology/ontology-requests/3352":https://sourceforge.net/p/geneontology/ontology-requests/3352

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This suggestion makes sense to me. Do you want to implement it, or should we?

m

Original comment by: mah11

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Hi Midori,

Thanks for the suggestion. I'll do it and get back in practice!

-karen

Original comment by: krchristie

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Original comment by: krchristie

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I've gone ahead and moved this term as I suggested.

I've also just noticed that this term has an is_a relationship to 'nuclear mRNA splicing, via spliceosome'. I'm not entirely sure this is always true. I'll try to find the paper I was reading a couple weeks ago that talked about some interplay between splicing of the 'host' mRNA versus snoRNA processing that occurred by a non-splicing mechanism and that prevented expression of the host mRNA.

-Karen

Original comment by: krchristie

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H Karen I would think that if there ARE instances of snoRNA processing from an intron that do not 1rst require the intron from being removed normally (and thus destroying the chance for the mRNA to become processed, or at least having THAT intron properly excised), then I would have to agree that the is_a link to nuclear mrNA splicing via spliceosome is not always true and thus the link should not exist.

Original comment by: hdrabkin

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Hi Harold,

I'm pretty sure that there "ARE instances of snoRNA processing from an intron that do not 1rst require the intron from being removed normally (and thus destroying the chance for the mRNA to become processed"

However, even for cases where the snoRNA is processed out of the lariat, I'm not sure that I would consider the 'intronic snoRNA processing' to be an instance of 'mRNA processing' because as I think of the process of mRNA processing, I'd think of the lariat as the byproduct that is released from the spliceosome. The further processing of the lariat to release the snoRNA is not mediated by the spliceosome and thus it doesn't really seem like 'intronic snoRNA processing' really has any relationship with 'mRNA processing, via spliceosome'.

Anyway, I'll check back with the snoRNA paper I was reading to confirm the facts.

-Karen

Original comment by: krchristie

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Hi,

The paper I was reading that listed various modes of snoRNA expression was this one:

Kruszka K, Barneche F, Guyot R, Ailhas J, Meneau I, Schiffer S, Marchfelder A, Echeverria M. (2003) EMBO J. 2003 Feb 3;22(3):621-32. PMID: 12554662

Here is a paragraph from the introduction of that paper. It mentions a couple different ways in which snoRNAs are released from the introns of protein- coding genes, and cites references.

"The snoRNAs have diverse modes of expression depending on the organism. In vertebrates most snoRNAs are nested within introns of protein coding genes and are produced by exonucleolytic processing of the debranched intron (Kiss and Filipowicz, 1995). An alternate pathway implicates direct endonucleolytic cleavage of the unspliced mRNA to release the intronic snoRNA (Villa et al., 1998; Giorgi et al., 2001). Usually host genes encode abundant house-keeping proteins related to ribosome biogenesis but there are exceptional cases of non-coding genes expressing intronic snoRNAs (Tycowski et al., 1996; Pelczar and Filipowicz, 1998). In yeast, many snoRNAs are encoded by independent monocistronic genes, but there are also five polycistronic genes and a few intronic snoRNAs (Lowe and Eddy, 1999). In Archaea many C/D RNAs guiding rRNA methylation have been identified encoded by individual genes (Gaspin et al., 2000; Omer et al., 2000). Interestingly, one exceptional case is an archaeal C/D snRNA nested in an intron of pre-tRNATrp that guides methylation in cis of the same tRNATrp (Clouet d’Orval et al., 2001)."

-Karen

Original comment by: krchristie

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Hi,

Below is another quote from a different paper, also from the introduction and with some references.

The more I think about this, the more convinced I am. While there is some relationship between 'intronic snoRNA processing' and 'mRNA splicing, via spliceosome', it is neither an is_a or part_of relationship, ever. If we could represent some sort of follows_after relationship, it would be OK if they were always processed out of the lariats, but that's not even true all the time.

If we get to where we allow GO to have more relationships, we could have something like this:

snoRNA metabolism is_a snoRNA processing .is_a intronic snoRNA processing ..is_a intronic snoRNA processing, via lariat debranching ..is_a intronic snoRNA processing, via endonucleolytic cleavage

nuclear mRNA splicing, via spliceosome .occurs_after intronic snoRNA processing, via lariat debranching .competes_with intronic snoRNA processing, via endonucleolytic cleavage

But for right now, since "intronic snoRNA processing" has neither an is_a or a part_of relationship with "nuclear mRNA splicing, via spliceosome"

I plan to remove this particular relationship.

In addition, I plan to make a minor change to the definition, which is currently this:

"The biogenesis of a snoRNA molecue which resides within, and is processed from, the intron of a mRNA."

The word 'mRNA' needs to be changed to 'pre-mRNA' because the 'mRNA', by definition no longer contains introns.

I plan to make these two changes on Monday May 29th, unless I hear objections.

thanks,

-Karen

Villa T, Ceradini F, Presutti C, Bozzoni I (1998) Processing of the intron- encoded U18 small nucleolar RNA in the yeast Saccharomyces cerevisiae relies on both exo- and endonucleolytic activities. Mol Cell Biol 18(6): 3376-83 PubMed ID: 9584178

The presence of snoRNAs within introns also raises the new issue of relating intronic snoRNA biosynthesis to processing of the host pre-mRNA. The biosynthetic mechanism of several intron-encoded snoRNAs has been investigated in vivo and in vitro, leading to the proposal of two alternative processing models. One model predicts that the snoRNA processing reaction is accomplished through the splicing pathway by exonucleolytic trimming of the spliced host intron after it has been debranched. Such a processing mechanism was originally suggested for human U17 and U19 (22). In fact, both of these snoRNAs are released from host and nonhost spliceable precursors in vivo, suggesting that the snoRNA coding regions contain all of the signals required for faithful excision. Exonucleolytic trimming has also been proposed for some other snoRNAs, such as the U15 (47) and U20 (8) snoRNAs. A different maturation pathway, based on endonucleolytic activity, has been proposed for the Xenopus laevis U16 and U18 snoRNAs, both of which are encoded within introns of the L1 ribosomal protein gene (10, 36). It has been demonstrated that they can be produced through a pathway, alternative to splicing, which involves endonucleolytic cleavage of the pre- mRNA (5, 6). This event is driven by two independent endonucleolytic cleavages within intron sequences upstream and downstream of the snoRNA coding region, producing 5′ and 3′ cutoff products; when both cleavages occur on the same precursor, pre-snoRNA molecules are produced that still contain 5′ and 3′ trailer sequences. Finally, exonucleolytic trimming converts the processing intermediates into mature snoRNA molecules.

5. Caffarelli E, Arese M, Santoro B, Fragapane P, Bozzoni I. In vitro study of processing of the intron-encoded U16 small nucleolar RNA in Xenopus laevis. Mol Cell Biol. 1994;14:2966–2974. 6. Caffarelli E, Fatica A, Prislei S, De Gregorio E, Fragapane P, Bozzoni I. Processing of the intron-encoded U16 and U18 snoRNAs: the conserved C and D boxes control both the processing reaction and the stability of the mature snoRNA. EMBO J. 1996;15:1121–1131.

Original comment by: krchristie

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Hi,

Below is another quote from a different paper, also from the introduction and with some references.

The more I think about this, the more convinced I am. While there is some relationship between 'intronic snoRNA processing' and 'mRNA splicing, via spliceosome', it is neither an is_a or part_of relationship, ever. If we could represent some sort of follows_after relationship, it would be OK if they were always processed out of the lariats, but that's not even true all the time.

If we get to where we allow GO to have more relationships, we could have something like this:

snoRNA metabolism is_a snoRNA processing .is_a intronic snoRNA processing ..is_a intronic snoRNA processing, via lariat debranching ..is_a intronic snoRNA processing, via endonucleolytic cleavage

nuclear mRNA splicing, via spliceosome .occurs_after intronic snoRNA processing, via lariat debranching .competes_with intronic snoRNA processing, via endonucleolytic cleavage

But for right now, since "intronic snoRNA processing" has neither an is_a or a part_of relationship with "nuclear mRNA splicing, via spliceosome"

I plan to remove this particular relationship.

In addition, I plan to make a minor change to the definition, which is currently this:

"The biogenesis of a snoRNA molecue which resides within, and is processed from, the intron of a mRNA."

The word 'mRNA' needs to be changed to 'pre-mRNA' because the 'mRNA', by definition no longer contains introns.

I plan to make these two changes on Monday May 29th, unless I hear objections.

thanks,

-Karen

Villa T, Ceradini F, Presutti C, Bozzoni I (1998) Processing of the intron- encoded U18 small nucleolar RNA in the yeast Saccharomyces cerevisiae relies on both exo- and endonucleolytic activities. Mol Cell Biol 18(6): 3376-83 PubMed ID: 9584178

The presence of snoRNAs within introns also raises the new issue of relating intronic snoRNA biosynthesis to processing of the host pre-mRNA. The biosynthetic mechanism of several intron-encoded snoRNAs has been investigated in vivo and in vitro, leading to the proposal of two alternative processing models. One model predicts that the snoRNA processing reaction is accomplished through the splicing pathway by exonucleolytic trimming of the spliced host intron after it has been debranched. Such a processing mechanism was originally suggested for human U17 and U19 (22). In fact, both of these snoRNAs are released from host and nonhost spliceable precursors in vivo, suggesting that the snoRNA coding regions contain all of the signals required for faithful excision. Exonucleolytic trimming has also been proposed for some other snoRNAs, such as the U15 (47) and U20 (8) snoRNAs. A different maturation pathway, based on endonucleolytic activity, has been proposed for the Xenopus laevis U16 and U18 snoRNAs, both of which are encoded within introns of the L1 ribosomal protein gene (10, 36). It has been demonstrated that they can be produced through a pathway, alternative to splicing, which involves endonucleolytic cleavage of the pre- mRNA (5, 6). This event is driven by two independent endonucleolytic cleavages within intron sequences upstream and downstream of the snoRNA coding region, producing 5′ and 3′ cutoff products; when both cleavages occur on the same precursor, pre-snoRNA molecules are produced that still contain 5′ and 3′ trailer sequences. Finally, exonucleolytic trimming converts the processing intermediates into mature snoRNA molecules.

5. Caffarelli E, Arese M, Santoro B, Fragapane P, Bozzoni I. In vitro study of processing of the intron-encoded U16 small nucleolar RNA in Xenopus laevis. Mol Cell Biol. 1994;14:2966–2974. 6. Caffarelli E, Fatica A, Prislei S, De Gregorio E, Fragapane P, Bozzoni I. Processing of the intron-encoded U16 and U18 snoRNAs: the conserved C and D boxes control both the processing reaction and the stability of the mature snoRNA. EMBO J. 1996;15:1121–1131.

Original comment by: krchristie

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Hi Karen; You are right that the relationship we would LIKE to convey is not quite is_a or part_of, but a kind of "depends_on", in that for the processing of some of the intronic snoRNAs, the lariat needs to be generated first (which is a part of mRNA processing); again, however, even then, not all processing of intronic snoRNAs need the lariat, so we are "stuck again". The ideal relationship is a "sometimes_depends_on" (argh!). or .."could_follow", or "could_depend_on" or might_depend_on. Clearly, the biggest enemy of ontologic purity is nature itself, which doesn't follow rules of logic, but uses whatever is available (paraphrasing a quote from Phil Sharp on RNA processing).

I think the changes you suggest are appropriate.

Original comment by: hdrabkin

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Hi Harold,

It sounds like we're in agreement on this, so I'll go ahead and remove the is_a relationship to "nuclear mRNA splicing, via spliceosome".

Continuing on the tangent of the possible relationships, it's obvious that the term 'intronic snoRNA processing' doesn't have a clear-cut relationship with 'nuclear mRNA splicing, via spliceosome', but I think that it could have child terms that do have clear-cut relationships, e.g.:

nuclear mRNA splicing, via spliceosome .occurs_after intronic snoRNA processing, via lariat debranching .competes_with intronic snoRNA processing, via endonucleolytic cleavage

but since we're not creating those types of relationships now, I'll just remove the is_a one for now.

-Karen

Original comment by: krchristie

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Hi,

Acted as agreed in this discussion:

1. Removed inappropriate parentage under "nuclear mRNA splicing, via spliceosome"

2. Modified definition so that it says "pre-mRNA" instead of "mRNA"

-Karen

Original comment by: krchristie

[gocentral]

• status: open --> closed-fixed

Original comment by: krchristie