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Source ontology files for the Gene Ontology
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miRNA gene silencing- some new terms and some tweaks #2112

Closed gocentral closed 9 years ago

gocentral commented 19 years ago

Hi,

I'm currently curating a set of papers on miRNAs, and would like to tweak a couple of definitions for existing terms, aswell as adding a couple of new terms.

I know there's been some recent SF entries and new terms in this section of the tree, so I'd appreciate any comments etc.

I'd like to broaden the definition of GO:0035195 since plant miRNAs work principally by inducing mRNA cleavage:

miRNA-mediated gene silencing ; GO:0035195 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. definition_reference: PMID:15066283 definition_reference: PMID:15066275 > Down regulation of gene expression through the action of microRNAs (miRNAs), endogenous 21-24 nucleotide small RNAs processed from stem-loop RNA precursors. Once incorporated into a RNA-induced silencing complex (RISC), miRNAs can downregulate gene expression by either of two posttranscriptional mechanisms: mRNA cleavage or translational repression. definition_reference: PMID:15066283 definition_reference: PMID:15066275 definition_reference: PMID:14744438

I'd like to make 2 new terms, to describe the 2 main outcomes of miRNA gene silencing

miRNA-mediated gene silencing ; GO:0035195 --%miRNA-mediated gene silencing, negative regulation of translation ; GO:NEW --%miRNA-mediated gene silencing, mRNA cleavage ; GO:NEW

negative regulation of translation ; GO:0016478 --%miRNA-mediated gene silencing, negative regulation of translation ; GO:NEW

mRNA cleavage ; GO:0006379 --%miRNA-mediated gene silencing, mRNA cleavage ; GO:NEW

miRNA-mediated gene silencing, negative regulation of translation ; GO:NEW The process by which microRNAs (miRNAs) block the translation of target mRNAs into proteins. Once incorporated into a RNA-induced silencing complex (RISC), a miRNA will typically repress translation if the miRNA imperfectly base-pairs with the 3' untranslated regions of target mRNAs. PMID:15196554 PMID:14744438

miRNA-mediated gene silencing, mRNA cleavage ; GO:NEW The process by which microRNAs (miRNAs) direct the cleavage of target mRNAs. Once incorporated into a RNA-induced silencing complex (RISC), a miRNA will typically direct cleavage by base pairing with near-perfect complementarity to the target mRNA. Many plant miRNAs downregulate gene expression through this mechanism. PMID:15196554 PMID:14744438

I think RNA-induced silencing complex ; GO:0016442 ; synonym:RISC complex should be moved from its unlocalized position, to be a child of cytoplasm ; GO:0005737 (see PMID:14744438).

Since the RISC can contain either siRNAs (for RNAi) or miRNAs, I'd like to broaden its definition:

name: RNA-induced silencing complex ; GO:0016442 def: "An RNA-protein complex that degrades mRNAs through the generation of a sequence-specific nuclease; the sequence specificity is determined by the 22-nucleotide RNA sequences derived by cleavage of double-stranded RNAs." [MEDLINE:20210771] exact_synonym: "RISC complex" [] is_a: GO:0005941 > A ribonucleoprotein complex that contains members of the Argonaute family of proteins, small interfering RNAs (siRNAs) or microRNAs (miRNAs), and miRNA or siRNA-complementary mRNAs, in addition to a number of accessory factors. The RISC complex is involved in posttranscriptional repression of gene expression through downregulation of translation or induction of mRNA degradation. PMID: 15145345

According to PMID:14744438, the micro-ribonucleoprotein complex (GO:0035068) may be a subtype of RISC complex (ie one that contains miRNAs rather than siRNAs). But I don't know if this is enough info to make GO:0035068 a child of GO:0016442. Possibly in the future, together with a new siRISC term.

I'd like to add a new term to describe miRISC assembly:

miRNA-mediated gene silencing ; GO:0035195 --%miRNA-mediated gene silencing, miRNA loading onto RISC ; GO:NEW

miRNA-mediated gene silencing, miRNA loading onto RISC ; GO:NEW broad synonym: miRISC assembly The transfer of a microRNA (miRNA) strand from a miRNA:miRNA duplex onto the RNA-initiated silencing complex (RISC). PMID:14744438

And a new term to describe pre-miRNA export from the nucleus:

RNA-nucleus export ; GO:0006405 --%pre-microRNA nucleus export ; GO:NEW

pre-microRNA nucleus export ; GO:NEW exact synonym: pre-miRNA nucleus export Transport of pre-microRNAs (pre-miRNAs) from the nucleus to the cytoplasm. Pre-miRNAs are a ~60-70 nucleotide stem loop intermediate in miRNA production, produced by the nuclear cleavage of a primary miRNA (pri-mRNA) transcript. Pre-miRNAs are transported from the nucleus to the cytoplasm where further cleavage occurs to produce a mature miRNA product. PMID:14744438

A small tweak to the definition of GO:0035196:

term: miRNA-mediated gene silencing, production of miRNAs ; GO:0035196 definition: 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. definition_reference: PMID:15066283 definition_reference: PMID:15066275 > Cleavage of stem-loop RNA precursors into microRNAs (miRNAs), a class of small RNAs that primarily silence genes by blocking the translation of mRNA transcripts into protein. definition_reference: PMID:15066283 definition_reference: PMID:15066275

And a couple of synonyms to add in:

primary microRNA processing ; GO:0031053 exact synonym: primary miRNA processing exact synonym: pri-miRNA processing

pre-microRNA processing ; GO:0031054 exact synonym: pre-miRNA processing

I'd like to do the edits at the end of next week (Fri 27th) if there's no changes.

thanks Becky

Reported by: beckyfoulger

Original Ticket: "geneontology/ontology-requests/2119":https://sourceforge.net/p/geneontology/ontology-requests/2119

gocentral commented 19 years ago

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Hi Becky,

Those all look like fine edits to me. A RISC-like complex (argonaute/ dicer/RNA) used to eliminate DNA sequences is found in the nucleus in ciliates, not the cytoplasm. But as the definition of RISC is written in GO, this complex isn't included. If more work in the field shows it should be, I'll suggest RISC be pushed back to 'intracellular' at a later time.

Nick

Original comment by: nastover

gocentral commented 19 years ago

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Hi Nick,

The RISC complex is currently just under 'unlocalized protein complex' . I can move it up to be a child of 'protein complex', and give it the extra parent 'intracellular' for the moment. When it's clearer, two terms can always be created later for cytoplasmic RISC in (most) metazoans and nuclear RISC (in ciliates).

thanks for the input! Becky

Original comment by: beckyfoulger

gocentral commented 19 years ago

Original comment by: beckyfoulger

gocentral commented 19 years ago

Logged In: YES user_id=482748

Done as described above. RNA-induced silencing complex ; GO:0016442 moved to be a child of intracellular.

New terms added as follows: GO:0035278 BF miRNA-mediated gene silencing, negative regulation of translation GO:0035279 BF miRNA-mediated gene silencing, mRNA cleavage GO:0035280 BF miRNA-mediated gene silencing, miRNA loading onto RISC GO:0035281 BF pre-microRNA nucleus export

Original comment by: beckyfoulger