MicroRNAs and other tiny endogenous RNAs in C. elegans.
BACKGROUND
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.


RESULTS
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.


CONCLUSIONS
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.
Ambros
Victor
V
Dartmouth Medical School, Department of Genetics, Hanover, NH 03755, USA. vambros@dartmouth.edu
Lee
Rosalind C
RC
Lavanway
Ann
A
Williams
Peter T
PT
Jewell
David
D
D000818:Animals; D001483:Base Sequence; D015152:Blotting, Northern / Q000379:methods; D017173:Caenorhabditis elegans / Q000196:embryology / Q000235:genetics* / Q000254:growth & development; D029742:Caenorhabditis elegans Proteins / Q000235:genetics; D003001:Cloning, Molecular; D018076:DNA, Complementary / Q000235:genetics; D015723:Gene Library; D020459:Genes, rRNA / Q000235:genetics; D016678:Genome; D035683:MicroRNAs / Q000737:chemistry / Q000145:classification / Q000235:genetics*; D008969:Molecular Sequence Data; D009690:Nucleic Acid Conformation; D009693:Nucleic Acid Hybridization / Q000379:methods; D016372:RNA, Antisense / Q000737:chemistry / Q000145:classification / Q000235:genetics; D022661:RNA, Untranslated / Q000737:chemistry / Q000145:classification / Q000235:genetics; D016415:Sequence Alignment; D012689:Sequence Homology, Nucleic Acid
D029742:Caenorhabditis elegans Proteins; D018076:DNA, Complementary; D035683:MicroRNAs; D016372:RNA, Antisense; D022661:RNA, Untranslated