Computational discovery of sense-antisense transcription in the human and mouse genomes
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CitationShendure, Jay and George M. Church. 2002. Computational discovery of sense-antisense transcription in the human and mouse genomes. Genome Biology 3(9): research0044.1-0044.14.
AbstractBackground: Overlapping but oppositely oriented transcripts have the potential to form senseantisense
perfect double-stranded (ds) RNA duplexes. Over recent years, the number and variety
of examples of mammalian gene-regulatory phenomena in which endogenous dsRNA duplexes
have been proposed or demonstrated to participate has greatly increased. These include genomic
imprinting, RNA interference, translational regulation, alternative splicing, X-inactivation and
RNA editing. We computationally mined public mouse and human expressed sequence tag (EST)
databases to search for additional examples of bidirectionally transcribed genomic regions.
Results: Our bioinformatics approach identified over 217 candidate overlapping transcriptional
units, almost all of which are novel. From experimental validation of a subset of our predictions
by orientation-specific RT-PCR, we estimate that our methodology has a specificity of 84% or
greater. In many cases, regions of sense-antisense overlap within the 5´- or 3´-untranslated
regions of a given transcript correlate with genomic patterns of mouse-human conservation.
Conclusions: Our results, in conjunction with the literature, bring the total number of predicted
and validated examples of overlapping but oppositely oriented transcripts to over 300. Several of
these cases support the hypothesis that a subset of the instances of substantial mouse-human
conservation in the 5´ and 3´ UTRs of transcripts might be explained in part by functionality of an
overlapping transcriptional unit.
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