RRC ID 28841
著者 Miki TS, Rüegger S, Gaidatzis D, Stadler MB, Großhans H.
タイトル Engineering of a conditional allele reveals multiple roles of XRN2 in Caenorhabditis elegans development and substrate specificity in microRNA turnover.
ジャーナル Nucleic Acids Res
Abstract Although XRN2 proteins are highly conserved eukaryotic 5'→3' exonucleases, little is known about their function in animals. Here, we characterize Caenorhabditis elegans XRN2, which we find to be a broadly and constitutively expressed nuclear protein. An xrn-2 null mutation or loss of XRN2 catalytic activity causes a molting defect and early larval arrest. However, by generating a conditionally mutant xrn-2ts strain de novo through an approach that may be also applicable to other genes of interest, we reveal further functions in fertility, during embryogenesis and during additional larval stages. Consistent with the known role of XRN2 in controlling microRNA (miRNA) levels, we can demonstrate that loss of XRN2 activity stabilizes some rapidly decaying miRNAs. Surprisingly, however, other miRNAs continue to decay rapidly in xrn-2ts animals. Thus, XRN2 has unanticipated miRNA specificity in vivo, and its diverse developmental functions may relate to distinct substrates. Finally, our global analysis of miRNA stability during larval stage 1 reveals that miRNA passenger strands (miR*s) are substantially less stable than guide strands (miRs), supporting the notion that the former are mostly byproducts of biogenesis rather than a less abundant functional species.
巻・号 42(6)
ページ 4056-67
公開日 2014-4-1
DOI 10.1093/nar/gkt1418
PII gkt1418
PMID 24445807
PMC PMC3973323
MeSH Alleles Animals Caenorhabditis elegans / enzymology Caenorhabditis elegans / genetics* Caenorhabditis elegans / growth & development Caenorhabditis elegans Proteins / genetics Caenorhabditis elegans Proteins / metabolism Caenorhabditis elegans Proteins / physiology* Exoribonucleases / genetics Exoribonucleases / metabolism Exoribonucleases / physiology* MicroRNAs / metabolism* Molting / genetics Mutagenesis, Site-Directed Mutation RNA Stability Substrate Specificity Temperature
IF 11.502
引用数 17
WOS 分野 BIOCHEMISTRY & MOLECULAR BIOLOGY
リソース情報
線虫 tm3473