Published online 24 June 2004
Nucleic Acids Research, Vol. 32 No. 11 © Oxford University Press 2004; all rights reserved
A probabilistic model of 3' end formation in Caenorhabditis elegans
Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridgeshire CB10 1SA, UK
* To whom correspondence should be addressed. Tel: +44 1223 834244; Fax: +44 1223 494919; Email: rd{at}sanger.ac.uk
The authors wish it to be known that, in their opinion, the first two authors should be regarded as joint First Authors
Received April 25, 2004; Revised and Accepted May 31, 2004
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.
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