Published online 9 September 2005
Article |
Extended base pair complementarity between U1 snRNA and the 5' splice site does not inhibit splicing in higher eukaryotes, but rather increases 5' splice site recognition
Institut für Virologie, Heinrich-Heine-Universität Düsseldorf Universitätsstr. 1, Geb. 22.21, D-40225 Düsseldorf, Germany 1Department of Microbiology and Molecular Genetics, School of Medicine, University of California Irvine, Irvine, CA 92697, USA
*To whom correspondence should be addressed. Tel: +49 211 81 12393; Fax: +49 211 81 12227; Email: schaal{at}uni-duesseldorf.de
Received July 6, 2005. Revised August 23, 2005. Accepted August 23, 2005.
Spliceosome formation is initiated by the recognition of the 5' splice site through formation of an RNA duplex between the 5' splice site and U1 snRNA. We have previously shown that RNA duplex formation between U1 snRNA and the 5' splice site can protect pre-mRNAs from degradation prior to splicing. This initial RNA duplex must be disrupted to expose the 5' splice site sequence for base pairing with U6 snRNA and to form the active spliceosome. Here, we investigated whether hyperstabilization of the U1 snRNA/5' splice site duplex interferes with splicing efficiency in human cell lines or nuclear extracts. Unlike observations in Saccharomyces cerevisiae, we demonstrate that an extended U1 snRNA/5' splice site interaction does not decrease splicing efficiency, but rather increases 5' splice site recognition and exon inclusion. However, low complementarity of the 5' splice site to U1 snRNA significantly increases exon skipping and RNA degradation. Although the splicing mechanisms are conserved between human and S.cerevisiae, these results demonstrate that distinct differences exist in the activation of the spliceosome.
Correspondence may also be addressed to Klemens Hertel. Tel: +1 949 824 2127; Fax: +1 949 824 8598; Email: khertel{at}uci.edu
The authors wish it to be known that, in their opinion, the first two authors should be regarded as joint First Authors
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