Essential Role for Endogenous siRNAs during Meiosis in Mouse Oocytes

Stein, P., Rozhkov, N. V., Li, F., Cardenas, F. L., Davydenk, O., Vandivier, L. E., Gregory, B. D., Hannon, G. J., Schultz, R. M. (February 2015) Essential Role for Endogenous siRNAs during Meiosis in Mouse Oocytes. PLoS Genetics, 11 (2). e1005013. ISSN 1553-7390

[img]
Preview
PDF (Paper)
Hannon PLoS Genetics 2015.pdf - Published Version

Download (1375Kb) | Preview
URL: http://www.ncbi.nlm.nih.gov/pubmed/25695507
DOI: 10.1371/journal.pgen.1005013

Abstract

The RNase III enzyme DICER generates both microRNAs (miRNAs) and endogenous short interfering RNAs (endo-siRNAs). Both small RNA species silence gene expression post-transcriptionally in association with the ARGONAUTE (AGO) family of proteins. In mammals, there are four AGO proteins (AGO1-4), of which only AGO2 possesses endonucleolytic activity. siRNAs trigger endonucleolytic cleavage of target mRNAs, mediated by AGO2, whereas miRNAs cause translational repression and mRNA decay through association with any of the four AGO proteins. Dicer deletion in mouse oocytes leads to female infertility due to defects during meiosis I. Because mouse oocytes express both miRNAs and endo-siRNAs, this phenotype could be due to the absence of either class of small RNA, or both. However, we and others demonstrated that miRNA function is suppressed in mouse oocytes, which suggested that endo-siRNAs, not miRNAs, are essential for female meiosis. To determine if this was the case we generated mice that express a catalytically inactive knock-in allele of Ago2 (Ago2ADH) exclusively in oocytes and thereby disrupted the function of siRNAs. Oogenesis and hormonal response are normal in Ago2ADH oocytes, but meiotic maturation is impaired, with severe defects in spindle formation and chromosome alignment that lead to meiotic catastrophe. The transcriptome of these oocytes is widely perturbed and shows a highly significant correlation with the transcriptome of Dicer null and Ago2 null oocytes. Expression of the mouse transcript (MT), the most abundant transposable element in mouse oocytes, is increased. This study reveals that endo-siRNAs are essential during meiosis I in mouse females, demonstrating a role for endo-siRNAs in mammals.

Item Type: Paper
Subjects: organs, tissues, organelles, cell types and functions > organelles, types and functions > meiosis
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > siRNA
CSHL Authors:
Communities: CSHL Cancer Center Program > Cancer Genetics
CSHL Cancer Center Shared Resources > Animal Services
CSHL labs > Hannon lab
CSHL Cancer Center Shared Resources > DNA Sequencing Service
Depositing User: Matt Covey
Date: 19 February 2015
Date Deposited: 27 Feb 2015 15:53
Last Modified: 05 Nov 2015 15:36
PMCID: PMC4335007
Related URLs:
URI: http://repository.cshl.edu/id/eprint/31247

Actions (login required)

Administrator's edit/view item Administrator's edit/view item
CSHL HomeAbout CSHLResearchEducationNews & FeaturesCampus & Public EventsCareersGiving