Published online 4 October 2005
Article |
Evidence for a preferential targeting of 3'-UTRs by cis-encoded natural antisense transcripts
Department of Medicine, Section of Hematology/Oncology, University of Chicago 5841 S. Maryland Avenue, MC2115, Chicago, IL 60637, USA 1Department of Biology and Biochemistry, University of Bath Somerset, BA2 7AY, UK 2Department of Genetics and Developmental Biology, University of Connecticut Health Center Farmington, CT 06030-3301, USA
*To whom correspondence should be addressed. Tel: +1 773 795 5474; Fax: +1 773 702 3002; Email: jchen{at}medicine.bsd.uchicago.edu
Received June 3, 2005. Revised August 4, 2005. Accepted September 5, 2005.
Although both the 5'- and 3'-untranslated regions (5'- and 3'-UTRs) of eukaryotic mRNAs may play a crucial role in posttranscriptional gene regulation, we observe that cis-encoded natural antisense RNAs have a striking preferential complementarity to the 3'-UTRs of their target genes in mammalian (human and mouse) genomes. A null neutral model, evoking differences in the rate of 3'-UTR and 5'-UTR extension, could potentially explain high rates of 3'-to-3' overlap compared with 5'-to-5' overlap. However, employing a simulation model we show that this null model probably cannot explain the finding that 3'-to-3' overlapping pairs have a much higher probability (>5 times) of conservation in both mouse and human genomes with the same overlapping pattern than do 5'-to-5' overlaps. Furthermore, it certainly cannot explain the finding that overlapping pairs seen in both genomes have a significantly higher probability of having co-expression and inverse expression (i.e. characteristic of senseantisense regulation) than do overlapping pairs seen in only one of the two species. We infer that the function of many 3'-to-3' overlaps is indeed antisense regulation. These findings underscore the preference for, and conservation of, 3'-UTR-targeted antisense regulation, and the importance of 3'-UTRs in gene regulation.
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