Abstract
In addition to several hundred microRNAs, C. elegans produces thousands of other small RNAs targeting coding genes, pseudogenes, transposons, and other noncoding RNAs. Here we review what is currently known about these endogenous small interfering RNAs (siRNAs) and piwi-interacting RNAs (piRNAs), providing an overview of their biogenesis, their associated protein factors, and their effects on mRNA dynamics and chromatin structure. Additionally, we describe how the molecular actions of these classes of endogenous small RNAs connect to their physiological roles in the organism.
Highlights
The phenomenon of RNA interference (RNAi), wherein introduction of double-stranded RNA (dsRNA) results in silencing of homologous genes, was first observed and reported in C. elegans
The preference shown by RDE-4 for binding of long dsRNA may promote exo-RNAi by aiding release of dsRNA small interfering RNAs (siRNAs) duplexes after DCR-1 processing (Parker et al, 2006), but argues against a role for RDE-4 in binding and stabilizing the likely very short dsRNA 26G RNA precursor
In the absence of exogenous dsRNA, RDE-1 binds a variety of DCR-1 products; among these are microRNAs and dsRNA-derived siRNAs cleaved from endogenous hairpins or bidirectionally transcribed genomic regions (Corrêa et al, 2010)
Summary
The phenomenon of RNA interference (RNAi), wherein introduction of dsRNA results in silencing of homologous genes, was first observed and reported in C. elegans. Among the species identified were a large pool of 5’ guanosine antisense small RNAs identified as endo-siRNAs that appeared to represent distinct 26- and 22-nucleotide (nt) subpopulations, later determined to correspond to primary and secondary endo-siRNAs, respectively (Ruby et al, 2006; Pak and Fire, 2007; Sijen et al, 2007; Han et al, 2009; Conine et al, 2010; Vasale et al, 2010) Subsequent dissection of these 26G and 22G RNA populations identified unique subgroups with largely overlapping biogenesis requirements but that engage different effector pathways distinguished by the particular Argonaute protein(s) interacting with the small RNAs. C. elegans encodes 27 Argonaute proteins. Whereas microRNAs are required for diverse developmental and physiological processes in the soma, endo-siRNAs and 21U RNAs serve as the guardians of the immortal germline, constituting a complex, interconnected, and tremendously robust system for surveillance of the C. elegans genome
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