Journal
RNA
Volume 19, Issue 9, Pages 1171-1182Publisher
COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT
DOI: 10.1261/rna.037630.112
Keywords
Drosophila; RNA-RNA; covariation; interaction network; long-range interactions
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Funding
- Frederick National Laboratory for Cancer Research, National Institutes of Health [HHSN261200800001E]
- Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research
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Functionally important nucleotide base-pairing often manifests itself in sequence alignments in the form of compensatory base changes (covariation). We developed a novel index-based computational method (CovaRNA) to detect long-range covariation on a genomic scale, as well as another computational method (CovStat) for determining the statistical significance of observed covariation patterns in alignment pairs. Here we present an all-versus-all search for nucleotide covariation in Drosophila genomic alignments. The search is genome wide, with the restriction that only alignments that correspond to euchromatic regions, which consist of at least 10 Drosophila species, are being considered (59% of the euchromatic genome of Drosophila melanogaster). We find that long-range covariations are especially prevalent between exons of mRNAs as well as noncoding RNAs; the majority of the observed covariations appear as not reverse complementary, but as synchronized mutations, which could be due to interactions with common interaction partners or due to the involvement of genomic elements that are antisense of annotated transcripts. The involved genes are enriched for functions related to regionalization as well as neural and developmental processes. These results are computational evidence that RNA-RNA long-range interactions are a widespread phenomenon that is of fundamental importance to a variety of cellular processes.
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