Show simple item record

dc.contributor.authorTabach, Yuvalen_US
dc.contributor.authorBilli, Allison C.en_US
dc.contributor.authorHayes, Gabriel D.en_US
dc.contributor.authorNewman, Martin A.en_US
dc.contributor.authorZuk, Oren_US
dc.contributor.authorGabel, Harrisonen_US
dc.contributor.authorKamath, Ravien_US
dc.contributor.authorYacoby, Kerenen_US
dc.contributor.authorChapman, Braden_US
dc.contributor.authorGarcia, Susana M.en_US
dc.contributor.authorBorowsky, Marken_US
dc.contributor.authorKim, John K.en_US
dc.contributor.authorRuvkun, Garyen_US
dc.date.accessioned2014-03-10T16:17:45Z
dc.date.issued2013en_US
dc.identifier.citationTabach, Y., A. C. Billi, G. D. Hayes, M. A. Newman, O. Zuk, H. Gabel, R. Kamath, et al. 2013. “Small RNA pathway genes identified by patterns of phylogenetic conservation and divergence.” Nature 493 (7434): 694-698. doi:10.1038/nature11779. http://dx.doi.org/10.1038/nature11779.en
dc.identifier.issn0028-0836en
dc.identifier.urihttp://nrs.harvard.edu/urn-3:HUL.InstRepos:11877132
dc.description.abstractGenetic and biochemical analyses of RNA interference (RNAi) and microRNA (miRNA) pathways have revealed proteins such as Argonaute/PIWI and Dicer that process and present small RNAs to their targets. Well validated small RNA pathway cofactors, such as the Argonaute/PIWI proteins show distinctive patterns of conservation or divergence in particular animal, plant, fungal, and protist species. We compared 86 divergent eukaryotic genome sequences to discern sets of proteins that show similar phylogenetic profiles with known small RNA cofactors. A large set of additional candidate small RNA cofactors have emerged from functional genomic screens for defects in miRNA- or siRNA-mediated repression in C. elegans and D. melanogaster1,2 and from proteomic analyses of proteins co-purifying with validated small RNA pathway proteins3,4. The phylogenetic profiles of many of these candidate small RNA pathway proteins are similar to those of known small RNA cofactor proteins. We used a Bayesian approach to integrate the phylogenetic profile analysis with predictions from diverse transcriptional coregulation and proteome interaction datasets to assign a probability for each protein for a role in a small RNA pathway. Testing high-confidence candidates from this analysis for defects in RNAi silencing, we found that about half of the predicted small RNA cofactors are required for RNAi silencing. Many of the newly identified small RNA pathway proteins are orthologues of proteins implicated in RNA splicing. In support of a deep connection between the mechanism of RNA splicing and small RNA-mediated gene silencing, the presence of the Argonaute proteins and other small RNA components in the many species analysed strongly correlates with the number of introns in that species.en
dc.language.isoen_USen
dc.relation.isversionofdoi:10.1038/nature11779en
dc.relation.hasversionhttp://www.ncbi.nlm.nih.gov/pmc/articles/PMC3762460/pdf/en
dash.licenseLAAen_US
dc.titleSmall RNA pathway genes identified by patterns of phylogenetic conservation and divergenceen
dc.typeJournal Articleen_US
dc.description.versionVersion of Recorden
dc.relation.journalNatureen
dash.depositing.authorTabach, Yuvalen_US
dc.date.available2014-03-10T16:17:45Z
dc.identifier.doi10.1038/nature11779*
dash.authorsorderedfalse
dash.contributor.affiliatedBorowsky, Mark L
dash.contributor.affiliatedTabach, Yuval
dash.contributor.affiliatedNewman, Martin
dash.contributor.affiliatedGarcia, Susana M. D. A.
dash.contributor.affiliatedGabel, Harrison
dash.contributor.affiliatedRuvkun, Gary


Files in this item

Thumbnail

This item appears in the following Collection(s)

Show simple item record