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A systematic search for RNA structural switches across the human transcriptome.
Khoroshkin, Matvei; Asarnow, Daniel; Zhou, Shaopu; Navickas, Albertas; Winters, Aidan; Goudreau, Jackson; Zhou, Simon K; Yu, Johnny; Palka, Christina; Fish, Lisa; Borah, Ashir; Yousefi, Kian; Carpenter, Christopher; Ansel, K Mark; Cheng, Yifan; Gilbert, Luke A; Goodarzi, Hani.
Afiliación
  • Khoroshkin M; Department of Biochemistry and Biophysics, University of California, San Francisco, San Francisco, CA, USA.
  • Asarnow D; Department of Urology, University of California, San Francisco, San Francisco, CA, USA.
  • Zhou S; Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, CA, USA.
  • Navickas A; Bakar Computational Health Sciences Institute, University of California, San Francisco, San Francisco, CA, USA.
  • Winters A; Department of Biochemistry and Biophysics, University of California, San Francisco, San Francisco, CA, USA.
  • Goudreau J; Department of Biochemistry, University of Washington, Seattle, WA, USA.
  • Zhou SK; Department of Biochemistry and Biophysics, University of California, San Francisco, San Francisco, CA, USA.
  • Yu J; Department of Urology, University of California, San Francisco, San Francisco, CA, USA.
  • Palka C; Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, CA, USA.
  • Fish L; Bakar Computational Health Sciences Institute, University of California, San Francisco, San Francisco, CA, USA.
  • Borah A; Department of Biochemistry and Biophysics, University of California, San Francisco, San Francisco, CA, USA.
  • Yousefi K; Department of Urology, University of California, San Francisco, San Francisco, CA, USA.
  • Carpenter C; Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, CA, USA.
  • Ansel KM; Bakar Computational Health Sciences Institute, University of California, San Francisco, San Francisco, CA, USA.
  • Cheng Y; Institut Curie, UMR3348 CNRS, U1278 Inserm, Orsay, France.
  • Gilbert LA; Department of Urology, University of California, San Francisco, San Francisco, CA, USA.
  • Goodarzi H; Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, CA, USA.
Nat Methods ; 2024 Jul 16.
Article en En | MEDLINE | ID: mdl-39014073
ABSTRACT
RNA structural switches are key regulators of gene expression in bacteria, but their characterization in Metazoa remains limited. Here, we present SwitchSeeker, a comprehensive computational and experimental approach for systematic identification of functional RNA structural switches. We applied SwitchSeeker to the human transcriptome and identified 245 putative RNA switches. To validate our approach, we characterized a previously unknown RNA switch in the 3' untranslated region of the RORC (RAR-related orphan receptor C) transcript. In vivo dimethyl sulfate (DMS) mutational profiling with sequencing (DMS-MaPseq), coupled with cryogenic electron microscopy, confirmed its existence as two alternative structural conformations. Furthermore, we used genome-scale CRISPR screens to identify trans factors that regulate gene expression through this RNA structural switch. We found that nonsense-mediated messenger RNA decay acts on this element in a conformation-specific manner. SwitchSeeker provides an unbiased, experimentally driven method for discovering RNA structural switches that shape the eukaryotic gene expression landscape.
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Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Idioma: En Revista: Nat Methods Asunto de la revista: TECNICAS E PROCEDIMENTOS DE LABORATORIO Año: 2024 Tipo del documento: Article País de afiliación: Estados Unidos
Texto completo
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Idioma: En Revista: Nat Methods Asunto de la revista: TECNICAS E PROCEDIMENTOS DE LABORATORIO Año: 2024 Tipo del documento: Article País de afiliación: Estados Unidos