The disparate nature of "intergenic" polyadenylation sites.
The termination of mature eukaryotic mRNAs occurs at specific polyadenylation sites located downstream from stop codons in the 3'-untranslated region (UTR). An accurate delineation of these sites is essential for the study of 3'-UTR-based gene regulation and for the design of pertinent probes for transcriptome analysis. Although typical poly(A) sites are located between 0 and 2 kb from the stop codon, EST sequence analyses have identified sites located at unexpectedly long ranges (5-10 kb) in a number of genes. Here we perform a complete mapping of EST and full-length cDNA sequences on the mouse and human genome to observe putative poly(A) sites extending beyond annotated 3'-ends and into the intergenic regions. We introduce several quality parameters for poly(A) site prediction and train a classification tree to associate P-values to predicted sites. We observe a higher than background level of high-scoring sites up to 12-15 kb past the stop codon, both in human and mouse. This leads to an estimate of about 5000 human genes having unreported 3'-end extensions and about 3500 novel polyadenylated transcripts lying in present "intergenic" regions. These high-scoring, long-range poly(A) sites corresponding to novel transcripts and gene extensions should be incorporated into current human and mouse gene repositories.
Lopez
Fabrice
F
Technologies Avancées pour le génome et la Clinique, ERM 206 INSERM, Université de la Méditerranée, Luminy Case 906, 13288 Marseille Cedex 09, France.
Granjeaud
Samuel
S
Ara
Takeshi
T
Ghattas
Badih
B
Gautheret
Daniel
D
D020413:3' Untranslated Regions / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D000818:Animals; D001483:Base Sequence; D001665:Binding Sites / Q000235:genetics; D018388:Codon, Terminator / Q000235:genetics; D019295:Computational Biology; D021901:DNA, Intergenic / Q000235:genetics; D020224:Expressed Sequence Tags; D006801:Humans; D051379:Mice; D012333:RNA, Messenger / Q000737:chemistry* / Q000235:genetics* / Q000378:metabolism; D014158:Transcription, Genetic
D020413:3' Untranslated Regions; D018388:Codon, Terminator; D021901:DNA, Intergenic; D012333:RNA, Messenger