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Abstract
MicroRNAs (miRNAs) are small noncoding RNAs that are processed from hairpin precursor
transcripts by Dicer. miRNAs probably inhibit translation of mRNAs via imprecise antisense
base-pairing. Small interfering RNAs (siRNAs) are similar in size to miRNAs, but they
recognize targets by precise complementarity and elicit RNA-mediated interference
(RNAi). We employed cDNA sequencing and comparative genomics to identify additional
C. elegans small RNAs with properties similar to miRNAs and siRNAs.
We found three broad classes of small RNAs in C. elegans: (1) 21 new miRNA genes (we
estimate that C. elegans contains approximately 100 distinct miRNA genes, about 30%
of which are conserved in vertebrates; (2), 33 distinct members of a class of tiny
noncoding RNA (tncRNA) genes with transcripts that are similar in length to miRNAs
(approximately 20-21 nt) and that are in some cases developmentally regulated but
are apparently not processed from a miRNA-like hairpin precursor and are not phylogenetically
conserved; (3) more than 700 distinct small antisense RNAs, about 20 nt long, that
are precisely complementary to protein coding regions of more than 500 different genes
and therefore seem to be endogenous siRNAs.
The presence of diverse endogenous siRNAs in normal worms suggests ongoing, genome-wide
gene silencing by RNAi. miRNAs and tncRNAs are not predicted to form complete Watson-Crick
hybrids with any C. elegans RNA target, and so they are likely to regulate the activity
of other genes by non-RNAi mechanisms. These results suggest that diverse modes of
small RNA-mediated gene regulation are deployed in normal worms.