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Engineering of a conditional allele reveals multiple roles of XRN2 in Caenorhabditis elegans development and substrate specificity in microRNA turnover

Miki, Takashi S., Rüegger, Stefan, Gaidatzis, Dimos, Stadler, Michael B., Großhans, Helge·2014·Nucleic Acids Research
DOI 10.1093/nar/gkt1418PMC PMC3973323
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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.

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  • Reduction of xrn-1 or xrn-2 affects the 5p/3p ratios of certain miRNAs.

    “Interestingly, this effect is not equal—reduction of xrn‐1 or xrn‐2 have been shown to affect the 5p/3p ratios of certain miRNAs (Chatterjee et al., 2011; Miki, Rüegger, Gaidatzis, Stadler, & Großhans, 2014).”

    From microRNA strand selection: Unwinding the rules (2021) · cites this paper as Miki, Rüegger, Gaidatzis, Stadler, & Großhans, 2014

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Research works printed but not linked: 51

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Authors
Miki, T. S., Rüegger, S., Gaidatzis, D., Stadler, M. B., & Großhans, H.
Affiliations
1 Friedrich Miescher Institute for Biomedical Research, Maulbeerstrasse 66, CH-4058 Basel, Switzerland, 2University of Basel, Petersplatz 1, CH-4003 Basel, Switzerland and 3Swiss Institute of Bioinformatics, Maulbeerstrasse 66, CH-4058 Basel, Switzerland
Venue
Nucleic Acids Research
Publisher
Oxford University Press (OUP)
Published
2014-01-20
Volume
42
Issue
6
Pages
4056-4067
ISSN
  • 1362-4962
  • 0305-1048
DOI
10.1093/nar/gkt1418
PMC
PMC3973323
Cited by
33
References
0
Language
en
Licence
creativecommons.org/licenses/by-nc/3.0/ (vor, 1026 d)

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