A probabilistic model of 3' end formation in Caenorhabditis elegans.
The 3' ends of mRNAs terminate with a poly(A) tail. This post-transcriptional modification is directed by sequence features present in the 3'-untranslated region (3'-UTR). We have undertaken a computational analysis of 3' end formation in Caenorhabditis elegans. By aligning cDNAs that diverge from genomic sequence at the poly(A) tract, we accurately identified a large set of true cleavage sites. When there are many transcripts aligned to a particular locus, local variation of the cleavage site over a span of a few bases is frequently observed. We find that in addition to the well-known AAUAAA motif there are several regions with distinct nucleotide compositional biases. We propose a generalized hidden Markov model that describes sequence features in C.elegans 3'-UTRs. We find that a computer program employing this model accurately predicts experimentally observed 3' ends even when there are multiple AAUAAA motifs and multiple cleavage sites. We have made available a complete set of polyadenylation site predictions for the C.elegans genome, including a subset of 6570 supported by aligned transcripts.
Hajarnavis
Ashwin
A
Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridgeshire CB10 1SA, UK.
Korf
Ian
I
Durbin
Richard
R
D020413:3' Untranslated Regions / Q000737:chemistry* / Q000378:metabolism*; D000818:Animals; D001483:Base Sequence; D017173:Caenorhabditis elegans / Q000235:genetics* / Q000378:metabolism; D019295:Computational Biology; D017238:Genes, Helminth; D008390:Markov Chains; D008957:Models, Genetic; D015233:Models, Statistical; D008969:Molecular Sequence Data; D009711:Nucleotides / Q000032:analysis; D011336:Probability; D039104:RNA 3' Polyadenylation Signals; D022821:RNA Splice Sites; D012326:RNA Splicing; D038621:Regulatory Sequences, Ribonucleic Acid; D013269:Stochastic Processes
D020413:3' Untranslated Regions; D009711:Nucleotides; D022821:RNA Splice Sites; D038621:Regulatory Sequences, Ribonucleic Acid