RRC ID 76008
Author Makeyeva YV, Shirayama M, Mello CC.
Title Cues from mRNA splicing prevent default Argonaute silencing in C. elegans.
Journal Dev Cell
Abstract In animals, Argonaute small-RNA pathways scan germline transcripts to silence self-replicating genetic elements. However, little is known about how endogenous gene expression is recognized and licensed. Here, we show that the presence of introns and, by inference, the process of mRNA splicing prevents default Argonaute-mediated silencing in the C. elegans germline. The silencing of intronless genes is initiated independently of the piRNA pathway but nevertheless engages multiple components of the downstream amplification and maintenance mechanisms that mediate transgenerational silencing, including both nuclear and cytoplasmic members of the worm-specific Argonaute gene family (WAGOs). Small RNAs amplified from intronless mRNAs can trans-silence cognate intron-containing genes. Interestingly, a second, small RNA-independent cis-acting mode of silencing also acts on intronless mRNAs. Our findings suggest that cues put in place during mRNA splicing license germline gene expression and provide evidence for a splicing-dependent and dsRNA- and piRNA-independent mechanism that can program Argonaute silencing.
Volume 56(18)
Pages 2636-2648.e4
Published 2021-9-27
DOI 10.1016/j.devcel.2021.08.022
PII S1534-5807(21)00681-X
PMID 34547227
PMC PMC8693449
MeSH Animals Argonaute Proteins / genetics* Caenorhabditis elegans / metabolism Caenorhabditis elegans Proteins / metabolism Cell Nucleus / metabolism Cues* Gene Silencing / physiology* Germ Cells / metabolism Nuclear Proteins / metabolism RNA Splicing / genetics RNA, Messenger / genetics* RNA, Small Interfering / genetics
C.elegans tm872