RRC ID 47317
Author Yang Z, Chen KM, Pandey RR, Homolka D, Reuter M, Janeiro BK, Sachidanandam R, Fauvarque MO, McCarthy AA, Pillai RS.
Title PIWI Slicing and EXD1 Drive Biogenesis of Nuclear piRNAs from Cytosolic Targets of the Mouse piRNA Pathway.
Journal Mol. Cell
Abstract PIWI-interacting RNAs (piRNAs) guide PIWI proteins to suppress transposons in the cytoplasm and nucleus of animal germ cells, but how silencing in the two compartments is coordinated is not known. Here we demonstrate that endonucleolytic slicing of a transcript by the cytosolic mouse PIWI protein MILI acts as a trigger to initiate its further 5'→3' processing into non-overlapping fragments. These fragments accumulate as new piRNAs within both cytosolic MILI and the nuclear MIWI2. We also identify Exonuclease domain-containing 1 (EXD1) as a partner of the MIWI2 piRNA biogenesis factor TDRD12. EXD1 homodimers are inactive as a nuclease but function as an RNA adaptor within a PET (PIWI-EXD1-Tdrd12) complex. Loss of Exd1 reduces sequences generated by MILI slicing, impacts biogenesis of MIWI2 piRNAs, and de-represses LINE1 retrotransposons. Thus, piRNA biogenesis triggered by PIWI slicing, and promoted by EXD1, ensures that the same guides instruct PIWI proteins in the nucleus and cytoplasm.
Volume 61(1)
Pages 138-52
Published 2016-1-7
DOI 10.1016/j.molcel.2015.11.009
PII S1097-2765(15)00869-2
PMID 26669262
PMC PMC4712191
MeSH Amino Acid Sequence Animals Argonaute Proteins / chemistry Argonaute Proteins / genetics Argonaute Proteins / metabolism* Carrier Proteins / metabolism Cell Nucleus / enzymology* Cytosol / enzymology* Drosophila Proteins / genetics Drosophila Proteins / metabolism Drosophila melanogaster / genetics Drosophila melanogaster / metabolism Exonucleases / chemistry Exonucleases / genetics Exonucleases / metabolism* Female Gene Expression Regulation Male Mice, Transgenic Models, Molecular Molecular Sequence Data Multiprotein Complexes Protein Interaction Domains and Motifs RNA Interference RNA Processing, Post-Transcriptional* RNA, Small Interfering / genetics RNA, Small Interfering / metabolism* RNA-Binding Proteins / chemistry RNA-Binding Proteins / genetics RNA-Binding Proteins / metabolism*
IF 14.248
Times Cited 8
WOS Category BIOCHEMISTRY & MOLECULAR BIOLOGY CELL BIOLOGY
Resource
Drosophila 11263R-1 11263R-2 11133R-1 31755R-1