A systematic search for RNA structural switches across the human transcriptome.

Autor:	Khoroshkin M; Department of Biochemistry and Biophysics, University of California, San Francisco, San Francisco, CA, USA.; Department of Urology, University of California, San Francisco, San Francisco, CA, USA.; Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, CA, USA.; Bakar Computational Health Sciences Institute, University of California, San Francisco, San Francisco, CA, USA., Asarnow D; Department of Biochemistry and Biophysics, University of California, San Francisco, San Francisco, CA, USA.; Department of Biochemistry, University of Washington, Seattle, WA, USA., Zhou S; Department of Biochemistry and Biophysics, University of California, San Francisco, San Francisco, CA, USA.; Department of Urology, University of California, San Francisco, San Francisco, CA, USA.; Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, CA, USA.; Bakar Computational Health Sciences Institute, University of California, San Francisco, San Francisco, CA, USA., Navickas A; Department of Biochemistry and Biophysics, University of California, San Francisco, San Francisco, CA, USA.; Department of Urology, University of California, San Francisco, San Francisco, CA, USA.; Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, CA, USA.; Bakar Computational Health Sciences Institute, University of California, San Francisco, San Francisco, CA, USA.; Institut Curie, UMR3348 CNRS, U1278 Inserm, Orsay, France., Winters A; Department of Urology, University of California, San Francisco, San Francisco, CA, USA.; Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, CA, USA.; Bakar Computational Health Sciences Institute, University of California, San Francisco, San Francisco, CA, USA.; Department of Biological and Medical Informatics, University of California, San Francisco, San Francisco, CA, USA.; Department of Cellular and Molecular Pharmacology, University of California, San Francisco, San Francisco, CA, USA.; Arc Institute, Palo Alto, CA, USA., Goudreau J; Department of Biochemistry and Biophysics, University of California, San Francisco, San Francisco, CA, USA.; Department of Urology, University of California, San Francisco, San Francisco, CA, USA.; Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, CA, USA.; Bakar Computational Health Sciences Institute, University of California, San Francisco, San Francisco, CA, USA., Zhou SK; Sandler Asthma Basic Research Center, University of California, San Francisco, San Francisco, CA, USA.; Department of Microbiology and Immunology, University of California, San Francisco, San Francisco, CA, USA., Yu J; Department of Biochemistry and Biophysics, University of California, San Francisco, San Francisco, CA, USA.; Department of Urology, University of California, San Francisco, San Francisco, CA, USA.; Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, CA, USA.; Bakar Computational Health Sciences Institute, University of California, San Francisco, San Francisco, CA, USA., Palka C; Gladstone Institute of Data Science and Biotechnology, San Francisco, CA, USA., Fish L; Department of Biochemistry and Biophysics, University of California, San Francisco, San Francisco, CA, USA.; Department of Urology, University of California, San Francisco, San Francisco, CA, USA.; Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, CA, USA.; 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.; Department of Urology, University of California, San Francisco, San Francisco, CA, USA.; Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, CA, USA.; Bakar Computational Health Sciences Institute, University of California, San Francisco, San Francisco, CA, USA., Yousefi K; Department of Biochemistry and Biophysics, University of California, San Francisco, San Francisco, CA, USA.; Department of Urology, University of California, San Francisco, San Francisco, CA, USA.; Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, CA, USA.; Bakar Computational Health Sciences Institute, University of California, San Francisco, San Francisco, CA, USA., Carpenter C; Department of Biochemistry and Biophysics, University of California, San Francisco, San Francisco, CA, USA.; Department of Urology, University of California, San Francisco, San Francisco, CA, USA.; Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, CA, USA.; Bakar Computational Health Sciences Institute, University of California, San Francisco, San Francisco, CA, USA., Ansel KM; Sandler Asthma Basic Research Center, University of California, San Francisco, San Francisco, CA, USA.; Department of Microbiology and Immunology, University of California, San Francisco, San Francisco, CA, USA., Cheng Y; Department of Biochemistry and Biophysics, University of California, San Francisco, San Francisco, CA, USA.; Howard Hughes Medical Institute, University of California San Francisco, San Francisco, CA, USA., Gilbert LA; Department of Urology, University of California, San Francisco, San Francisco, CA, USA.; Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, CA, USA.; Department of Cellular and Molecular Pharmacology, University of California, San Francisco, San Francisco, CA, USA.; Arc Institute, Palo Alto, CA, USA., Goodarzi H; Department of Biochemistry and Biophysics, University of California, San Francisco, San Francisco, CA, USA. hani.goodarzi@ucsf.edu.; Department of Urology, University of California, San Francisco, San Francisco, CA, USA. hani.goodarzi@ucsf.edu.; Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, CA, USA. hani.goodarzi@ucsf.edu.; Bakar Computational Health Sciences Institute, University of California, San Francisco, San Francisco, CA, USA. hani.goodarzi@ucsf.edu.; Arc Institute, Palo Alto, CA, USA. hani.goodarzi@ucsf.edu.
Jazyk:	angličtina
Zdroj:	Nature methods [Nat Methods] 2024 Sep; Vol. 21 (9), pp. 1634-1645. Date of Electronic Publication: 2024 Jul 16.
DOI:	10.1038/s41592-024-02335-1
Abstrakt:	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. (© 2024. The Author(s).)
Databáze:	MEDLINE
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