National Institutes of Health/National Institute of General Medical Sciences (NIH/NIGMS)
1R35GM140847
米国
National Institutes of Health/National Institute of General Medical Sciences (NIH/NIGMS)
S10OD020054
米国
National Institutes of Health/National Institute of General Medical Sciences (NIH/NIGMS)
S10OD021741
米国
National Institutes of Health/National Institute of General Medical Sciences (NIH/NIGMS)
S10OD026881
米国
Howard Hughes Medical Institute (HHMI)
米国
National Institutes of Health/National Cancer Institute (NIH/NCI)
R01CA240984
米国
National Institutes of Health/National Cancer Institute (NIH/NCI)
R01CA244634
米国
引用
ジャーナル: Nat Methods / 年: 2024 タイトル: A systematic search for RNA structural switches across the human transcriptome. 著者: Matvei Khoroshkin / Daniel Asarnow / Shaopu Zhou / Albertas Navickas / Aidan Winters / Jackson Goudreau / Simon K Zhou / Johnny Yu / Christina Palka / Lisa Fish / Ashir Borah / Kian Yousefi / ...著者: Matvei Khoroshkin / Daniel Asarnow / Shaopu Zhou / Albertas Navickas / Aidan Winters / Jackson Goudreau / Simon K Zhou / Johnny Yu / Christina Palka / Lisa Fish / Ashir Borah / Kian Yousefi / Christopher Carpenter / K Mark Ansel / Yifan Cheng / Luke A Gilbert / Hani Goodarzi / 要旨: 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 ...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.