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Extensive Structural Differences of Closely Related 3' mRNA Isoforms: Links to Pab1 Binding and mRNA Stability.
Moqtaderi, Zarmik; Geisberg, Joseph V; Struhl, Kevin.
Afiliação
  • Moqtaderi Z; Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA 02115, USA.
  • Geisberg JV; Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA 02115, USA.
  • Struhl K; Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA 02115, USA. Electronic address: kevin@hms.harvard.edu.
Mol Cell ; 72(5): 849-861.e6, 2018 12 06.
Article em En | MEDLINE | ID: mdl-30318446
Alternative polyadenylation generates numerous 3' mRNA isoforms that can vary in biological properties, such as stability and localization. We developed methods to obtain transcriptome-scale structural information and protein binding on individual 3' mRNA isoforms in vivo. Strikingly, near-identical mRNA isoforms can possess dramatically different structures throughout the 3' UTR. Analyses of identical mRNAs in different species or refolded in vitro indicate that structural differences in vivo are often due to trans-acting factors. The level of Pab1 binding to poly(A)-containing isoforms is surprisingly variable, and differences in Pab1 binding correlate with the extent of structural variation for closely spaced isoforms. A pattern encompassing single-strandedness near the 3' terminus, double-strandedness of the poly(A) tail, and low Pab1 binding is associated with mRNA stability. Thus, individual 3' mRNA isoforms can be remarkably different physical entities in vivo. Sequences responsible for isoform-specific structures, differential Pab1 binding, and mRNA stability are evolutionarily conserved, indicating biological function.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Saccharomyces cerevisiae / RNA Fúngico / RNA Mensageiro / Regulação Fúngica da Expressão Gênica / Proteínas de Saccharomyces cerevisiae / Proteínas de Ligação a Poli(A) / Isoformas de RNA Idioma: En Ano de publicação: 2018 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Saccharomyces cerevisiae / RNA Fúngico / RNA Mensageiro / Regulação Fúngica da Expressão Gênica / Proteínas de Saccharomyces cerevisiae / Proteínas de Ligação a Poli(A) / Isoformas de RNA Idioma: En Ano de publicação: 2018 Tipo de documento: Article