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Nucleic Acids Res. 2005 Oct 4;33(17):5533-43. Print 2005.

Evidence for a preferential targeting of 3'-UTRs by cis-encoded natural antisense transcripts.

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  • 1Department of Medicine, Section of Hematology/Oncology, University of Chicago, 5841 S. Maryland Avenue, MC2115, Chicago, IL 60637, USA.

Abstract

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 sense-antisense 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.

PMID:
16204454
[PubMed - indexed for MEDLINE]
PMCID:
PMC1243798
Free PMC Article

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