title: Evidence for a preferential targeting of 3'-UTRs by cis-encoded natural antisense transcripts.
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.
authors.affiliation: Department of Medicine, Section of Hematology/Oncology, University of Chicago, 5841 S. Maryland Avenue, MC2115, Chicago, IL 60637, USA.
authors.forename: Miao
authors.initials: M
authors.lastname: Sun
authors.forename: Laurence D
authors.initials: LD
authors.lastname: Hurst
authors.forename: Gordon G
authors.initials: GG
authors.lastname: Carmichael
authors.forename: Jianjun
authors.initials: J
authors.lastname: Chen
mesh_terms: D020413:3' Untranslated Regions; D020121:5' Untranslated Regions; D000818:Animals; D020029:Base Pairing; D001665:Binding Sites; D019143:Evolution, Molecular; D005786:Gene Expression Regulation; D023281:Genomics; D006801:Humans; D051379:Mice; D008957:Models, Genetic; D012313:RNA / Q000096:biosynthesis / Q000235:genetics; D016372:RNA, Antisense / Q000096:biosynthesis / Q000235:genetics*
chemical_list: D020413:3' Untranslated Regions; D020121:5' Untranslated Regions; D016372:RNA, Antisense; D012313:RNA