MBE Advance Access published online on January 22, 2007
Molecular Biology and Evolution, doi:10.1093/molbev/msm010
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Position of the Final Intron in Full-Length Transcripts : Determined By NMD?
Department of Biology, Indiana University, 1001 East Third Street, Bloomington, Indiana 47405-3700 USA
* Corresponding author. E-mail: dgscofie{at}indiana.edu, Fax: 812-855-6705
Accepted for publication January 18, 2007.
Nonsense-mediated decay (NMD) pathways for detection and degradation of transcripts containing premature termination (stop) codons (PTCs) are ubiquitous among the eukaryotes. NMD uses the presence of a second signal downstream of a termination codon to distinguish a PTC from a true stop codon. In mammals and perhaps other eukaryotes, the second signal is a protein complex closely associated with exon-exon junctions formed after removal of spliceosomal introns. A valid transcript in such species must have its 3'-most intron positioned so as not to serve as a second signal relative to the true stop. This requirement has been termed the 55-bp rule, in reference to the position within the 3' untranslated region (3' UTR) of valid transcripts downstream of which introns should not be found. However, as more information has become available, it is apparent that the 55-bp rule still holds in species with NMD pathways which are not intron-dependent. To clarify the applicability of the 55-bp rule, we constructed a large database of 3'-most intron positions within full-length transcripts from four eukaryotes, two of which (human and mouse) use intron positions for NMD, one of which (Drosophila melanogaster) does not, and one of which (Arabidopsis thaliana) may not use intron positions. Surprisingly, we found intron numbers to be sharply reduced within 3' UTRs in comparison to coding sequences starting immediately downstream of true stop, rather than 55 bp; this strong threshold existed for all four species. We suggest that a more general mechanism higher rates of intron inclusion within 3' UTRs is better able to explain this threshold. We propose that 3' UTRs are better able to tolerate loss of intron integrity than other gene regions, due to the generally greater length of conserved sequences important within 3' UTR exons. This mechanism may also help to explain the roughly 3x greater length of 3' UTRs in comparison to 5' UTRs.
Key Words: intron nonsense-mediated decay 3' UTR 55-bp rule premature termination codon intron inclusion
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