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A novel role for nucleolin in splice site selection.
Shefer, Kinneret; Boulos, Ayub; Gotea, Valer; Arafat, Maram; Ben Chaim, Yair; Muharram, Aya; Isaac, Sara; Eden, Amir; Sperling, Joseph; Elnitski, Laura; Sperling, Ruth.
Afiliação
  • Shefer K; Department of Genetics, The Hebrew University of Jerusalem, Jerusalem Israel.
  • Boulos A; Department of Genetics, The Hebrew University of Jerusalem, Jerusalem Israel.
  • Gotea V; Translational and Functional Genomics Branch, National Human Genome Research Institute, NIH, Bethesda, MD USA.
  • Arafat M; Department of Genetics, The Hebrew University of Jerusalem, Jerusalem Israel.
  • Ben Chaim Y; Department of Natural Sciences, The Open University, Raanana Israel.
  • Muharram A; Department of Genetics, The Hebrew University of Jerusalem, Jerusalem Israel.
  • Isaac S; Department of Cell and Developmental Biology, The Hebrew University of Jerusalem, Jerusalem Israel.
  • Eden A; Department of Cell and Developmental Biology, The Hebrew University of Jerusalem, Jerusalem Israel.
  • Sperling J; Department of Organic Chemistry, The Weizmann Institute of Science, Rehovot Israel.
  • Elnitski L; Translational and Functional Genomics Branch, National Human Genome Research Institute, NIH, Bethesda, MD USA.
  • Sperling R; Department of Genetics, The Hebrew University of Jerusalem, Jerusalem Israel.
RNA Biol ; 19(1): 333-352, 2022.
Article em En | MEDLINE | ID: mdl-35220879
Latent 5' splice sites, not normally used, are highly abundant in human introns, but are activated under stress and in cancer, generating thousands of nonsense mRNAs. A previously proposed mechanism to suppress latent splicing was shown to be independent of NMD, with a pivotal role for initiator-tRNA independent of protein translation. To further elucidate this mechanism, we searched for nuclear proteins directly bound to initiator-tRNA. Starting with UV-crosslinking, we identified nucleolin (NCL) interacting directly and specifically with initiator-tRNA in the nucleus, but not in the cytoplasm. Next, we show the association of ini-tRNA and NCL with pre-mRNA. We further show that recovery of suppression of latent splicing by initiator-tRNA complementation is NCL dependent. Finally, upon nucleolin knockdown we show activation of latent splicing in hundreds of coding transcripts having important cellular functions. We thus propose nucleolin, a component of the endogenous spliceosome, through its direct binding to initiator-tRNA and its effect on latent splicing, as the first protein of a nuclear quality control mechanism regulating splice site selection to protect cells from latent splicing that can generate defective mRNAs.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Limite: Humans Idioma: En Ano de publicação: 2022 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Limite: Humans Idioma: En Ano de publicação: 2022 Tipo de documento: Article