NTR: lncRNA-mediated gene silencing

[RLovering]

Please provide as much information as you can:

• Suggested term label:lncRNA-mediated gene silencing

• Definition (free text) A post-transcriptional gene silencing pathway in which regulatory long noncoding RNAs (lncRNAs) elicit silencing of specific target genes, often miRNAs.

• Reference, in format PMID:####### PMID:34454184

• Gene product name and ID to be annotated to this term Homo-sapiens MIAT URS00007E4AF8_9606

• Parent term(s)

• is a child of GO:0035194 post-transcriptional gene silencing by RNA

• Children terms (if applicable) Should any existing terms that should be moved underneath this new proposed term?

• Synonyms (please specify, EXACT, BROAD, NARROW or RELATED)

• Cross-references

• For enzymes, please provide RHEA and/or EC numbers.

• Can also provide MetaCyc, KEGG, Wikipedia, and other links.

• Any other information see request https://github.com/geneontology/go-ontology/issues/23018 for positive regulation of lncRNA catabolism and https://github.com/geneontology/go-ontology/issues/22441 for this MF term

Homo-sapiens MIAT URS00007E4AF8_9606 is a long noncoding RNA that binds to Homo-sapiens hsa-miR-665 URS0000355E82_9606 and causes it to be degraded. Protein are involved in the degradation therefore I have included this term as a process not just a function

[pgaudet]

+[Term] +id: GO:0000512 +name: lncRNA-mediated gene silencing +namespace: biological_process +def: "A post-transcriptional gene silencing pathway in which regulatory long noncoding RNAs (lncRNAs) elicit silencing of specific target genes, often miRNAs." [PMID:34454184] +is_a: GO:0035194 ! post-transcriptional gene silencing by RNA +property_value: term_tracker_item https://github.com/geneontology/go-ontology/issues/23020 xsd:anyURI +created_by: pg +creation_date: 2022-03-16T07:57:55Z +

[RLovering]

• [x] please would you add the following comment: This term should be applied to lncRNAs and proteins associated with this process and not to the target (miR or mRNA) of the process

[ValWood]

I will also use for PMID:34389684 (I sill need https://github.com/geneontology/go-ontology/issues/22717 for this paper)

and a nice review that would make an additional ref for this term. Long RNA-Mediated Chromatin Regulation in Fission Yeast and Mammals PMID:35055152

[ValWood]

Actually the parentage needs revising. The lncRNA-mediated gene silencing in PMID:34389684 is transcriptional, not post-transcriptional.

Or you need to change the this term to "post-transcriptional lncRNA-mediated gene silencing"

(most lncRNA-mediated gene silencing that I'm aware of is transcriptional)

[pgaudet]

@ValWood so I would also create 'co-transcriptional lncRNA-mediated gene silencing' for PMID:34389684?

[ValWood]

The ones I have are 'transcriptional' but not co -transcriptional. I belive co-transcription occurs during transcription and processing? This is a bit different. The ncRNA prevents transcription (it is itself regulated destroyed by differential processing events. It is referred to as "transcriptional gene silencing"

[hattrill]

tagging @gantonazzo

[ValWood]

This seems to be

g, lncRNAs interfere with Pol II transcription machineries both at the initiation (left) and elongation (right) stages. in https://github.com/geneontology/go-ontology/issues/23028 (specifically left, iniitiation)

[RLovering]

I have added the link to g, but this request is for the BP term, the other ticket is for MFs (primarily) but also trying to check that we can apply all 3 aspects to cover these activities

[RLovering]

I think it would be good to try to replicate the existing ontology structure and term constructions so I would like to keep this as GO:0000512 +name: lncRNA-mediated gene silencing +def: "A post-transcriptional gene silencing pathway in which regulatory long noncoding RNAs (lncRNAs) elicit silencing of specific target genes, often miRNAs." [PMID:34454184] +is_a: GO:0035194 ! post-transcriptional gene silencing by RNA

which mirrors the ontology and definitions for GO:0035195 miRNA-mediated gene silencing

Note that in human there appear to be many lncRNAs that act as sponges to miRs and mRNAs

I think that a new term is needed for the BPs describing the lncRNAs acting at the level of transcription regulation and chromatin organization. We also need to consider whether these lncRNAs could be assigned existing GO terms that were created for the annotation of proteins - we shouldn't/may not need to create new terms just because these are RNAs. I guess that is why I wanted to focus on creating MF terms first because the activity of a RNA may not be appropriately captured by protein MFs.

[RLovering]

I guess the term Val is after should have the parent: GO:0140458 pre-transcriptional gene silencing by RNA which currently has the child terms: GO:0061587 transfer RNA gene-mediated silencing GO:0080188 gene silencing by RNA-directed DNA methylation

But the term 'transcriptional gene silencing' might need to be a bit more descriptive?

[pgaudet]

@ValWood For the paper you describe (PMID:34389684), @RLovering @gantonazzo and I propose you use BPs:

• GO:0060633 negative regulation of transcription initiation by RNA polymerase II
• and GO:0034244 negative regulation of transcription elongation by RNA polymerase II

If this is OK, please close.

Thanks, Pascale

[ValWood]

Right so there will be no terms for ncRNA-mediated gene silencing (presumably because the entity is a lncRNA so it unnecessary to capture this in a term? is that correct?

[pgaudet]

Hi @ValWood

Right so there will be no terms for ncRNA-mediated gene silencing (presumably because the entity is a lncRNA so it unnecessary to capture this in a term? is that correct?

No, we decided that these were different pathways and that we'd keep them all.

Please reopen if there is still anything to do here.