Conserved RNA secondary structures promote alternative splicing.
Pre-mRNA splicing is carried out by the spliceosome, which identifies exons and removes intervening introns. Alternative splicing in higher eukaryotes results in the generation of multiple protein isoforms from gene transcripts. The extensive alternative splicing observed implies a flexibility of the spliceosome to identify exons within a given pre-mRNA. To reach this flexibility, splice-site selection in higher eukaryotes has evolved to depend on multiple parameters such as splice-site strength, splicing regulators, the exon/intron architecture, and the process of pre-mRNA synthesis itself. RNA secondary structures have also been proposed to influence alternative splicing as stable RNA secondary structures that mask splice sites are expected to interfere with splice-site recognition. Using structural and functional conservation, we identified RNA structure elements within the human genome that associate with alternative splice-site selection. Their frequent involvement with alternative splicing demonstrates that RNA structure formation is an important mechanism regulating gene expression and disease.
Shepard
Peter J
PJ
Department of Microbiology and Molecular Genetics, Institute for Genomics and Bioinformatics, University of California at Irvine, Irvine, California 92697-4025, USA.
Hertel
Klemens J
KJ
D000465:Algorithms; D017398:Alternative Splicing; D000818:Animals; D001483:Base Sequence; D015894:Genome, Human; D006801:Humans; D009690:Nucleic Acid Conformation; D012313:RNA / Q000737:chemistry / Q000378:metabolism*; D022821:RNA Splice Sites; D016415:Sequence Alignment
D022821:RNA Splice Sites; D012313:RNA