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| Subject Categories: RNA |
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| The EMBO Journal
(2008) 27, 122–131, doi:10.1038/sj.emboj.7601957 Published online 13 December 2007 |
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| Intrasplicing coordinates alternative first exons with alternative splicing in the protein 4.1R gene |
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| Marilyn K Parra1, 3, Jeff S Tan1, 3, Narla Mohandas2 and John G Conboy1 |
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1 Life Sciences Division, Lawrence Berkeley National Laboratory, Berkeley, CA, USA 2 Red Cell Physiology Laboratory, New York Blood Center, New York, NY, USA To whom correspondence should be addressed John G Conboy, Life Sciences Division, Lawrence Berkeley National Laboratory, Building 74-157, Room 225 (MS 74-217), One Cyclotron Road, Berkeley, CA 94720, USA. Tel.: +1 510 486 6973; Fax: +1 510 486 6746; E-mail: jgconboy@lbl.gov 3 These authors contributed equally to this work Received 27 June 2007; Accepted 19 November 2007; Published online 13 December 2007. |
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| Abstract |
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| In the protein 4.1R gene, alternative first exons splice differentially to alternative 3' splice sites far downstream in exon 2'/2 (E2'/2). We describe a novel intrasplicing mechanism by which exon 1A (E1A) splices exclusively to the distal E2'/2 acceptor via two nested splicing reactions regulated by novel properties of exon 1B (E1B). E1B behaves as an exon in the first step, using its consensus 5' donor to splice to the proximal E2'/2 acceptor. A long region of downstream intron is excised, juxtaposing E1B with E2'/2 to generate a new composite acceptor containing the E1B branchpoint/pyrimidine tract and E2 distal 3' AG-dinucleotide. Next, the upstream E1A splices over E1B to this distal acceptor, excising the remaining intron plus E1B and E2' to form mature E1A/E2 product. We mapped branchpoints for both intrasplicing reactions and demonstrated that mutation of the E1B 5' splice site or branchpoint abrogates intrasplicing. In the 4.1R gene, intrasplicing ultimately determines N-terminal protein structure and function. More generally, intrasplicing represents a new mechanism by which alternative promoters can be coordinated with downstream alternative splicing. |
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| Keywords: alternative first exons, alternative splicing, intrasplicing, protein 4.1R |
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Top of page MORE ARTICLES LIKE THISThese links to content published by NPG are automatically generated NEWS AND VIEWSNature Biotechnology Research News (01 Jan 2002) Molecular biology: Excision of introns in lariat form Nature News and Views (13 Sep 1984) RESEARCHJournal of Cerebral Blood Flow & Metabolism Original Article Intrasplicing coordinates alternative first exons with alternative splicing in the protein 4.1R gene The EMBO Journal Article |
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