26G endo-siRNAs regulate spermatogenic and zygotic gene expression in Caenorhabditis elegans.
Endogenous small interfering RNAs (endo-siRNAs) regulate diverse gene expression programs in eukaryotes by either binding and cleaving mRNA targets or mediating heterochromatin formation; however, the mechanisms of endo-siRNA biogenesis, sorting, and target regulation remain poorly understood. Here we report the identification and function of a specific class of germline-generated endo-siRNAs in Caenorhabditis elegans that are 26 nt in length and contain a guanine at the first nucleotide position (i.e., 26G RNAs). 26G RNAs regulate gene expression during spermatogenesis and zygotic development, and their biogenesis requires the ERI-1 exonuclease and the RRF-3 RNA-dependent RNA polymerase (RdRP). Remarkably, we identified two nonoverlapping subclasses of 26G RNAs that sort into specific RNA-induced silencing complexes (RISCs) and differentially regulate distinct mRNA targets. Class I 26G RNAs target genes are expressed during spermatogenesis, whereas class II 26G RNAs are maternally inherited and silence gene expression during zygotic development. These findings implicate a class of endo-siRNAs in the global regulation of transcriptional programs required for fertility and development.
Life Sciences Institute, University of Michigan, Ann Arbor, MI 48109, USA.
Ting
T
Han
Arun Prasad
AP
Manoharan
Tim T
TT
Harkins
Pascal
P
Bouffard
Colin
C
Fitzpatrick
Diana S
DS
Chu
Danielle
D
Thierry-Mieg
Jean
J
Thierry-Mieg
John K
JK
Kim
D000818:Animals; D017173:Caenorhabditis elegans / Q000196:embryology* / Q000235:genetics*; D029742:Caenorhabditis elegans Proteins / Q000378:metabolism; D005095:Exoribonucleases / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D020868:Gene Silencing; D005854:Germ Cells / Q000378:metabolism; D006147:Guanine / Q000378:metabolism*; D008297:Male; D018510:RNA, Helminth / Q000145:classification / Q000378:metabolism; D034741:RNA, Small Interfering / Q000096:biosynthesis / Q000145:classification / Q000378:metabolism*; D017422:Sequence Analysis, DNA; D013091:Spermatogenesis / Q000235:genetics*; D015053:Zygote / Q000378:metabolism*
D029742:Caenorhabditis elegans Proteins; D018510:RNA, Helminth; D034741:RNA, Small Interfering; D006147:Guanine; C482202:ERI-1 protein, C elegans; D005095:Exoribonucleases