Intrasplicing coordinates alternative first exons with alternative splicing in the protein 4.1R gene

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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' ... continued below

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Conboy, John G.; Parra, Marilyn K.; Tan, Jeff S.; Mohandas, Narla & Conboy, John G. November 7, 2008.

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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 branch points 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 whereby alternative promoters can be coordinated with downstream alternative splicing.

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  • Journal Name: European Molecular Biology Organization Journal; Journal Volume: 27; Journal Issue: 1

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  • Report No.: LBNL-838E
  • Grant Number: DE-AC02-05CH11231
  • Office of Scientific & Technical Information Report Number: 936522
  • Archival Resource Key: ark:/67531/metadc902603

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Office of Scientific & Technical Information Technical Reports

Reports, articles and other documents harvested from the Office of Scientific and Technical Information.

Office of Scientific and Technical Information (OSTI) is the Department of Energy (DOE) office that collects, preserves, and disseminates DOE-sponsored research and development (R&D) results that are the outcomes of R&D projects or other funded activities at DOE labs and facilities nationwide and grantees at universities and other institutions.

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  • November 7, 2008

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  • Sept. 27, 2016, 1:39 a.m.

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  • Oct. 3, 2016, 1:49 p.m.

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Conboy, John G.; Parra, Marilyn K.; Tan, Jeff S.; Mohandas, Narla & Conboy, John G. Intrasplicing coordinates alternative first exons with alternative splicing in the protein 4.1R gene, article, November 7, 2008; Berkeley, California. (digital.library.unt.edu/ark:/67531/metadc902603/: accessed January 19, 2018), University of North Texas Libraries, Digital Library, digital.library.unt.edu; crediting UNT Libraries Government Documents Department.