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Title | A systematic search for RNA structural switches across the human transcriptome. |
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Journal, issue, pages | Nat Methods, Year 2024 |
Publish date | Jul 16, 2024 |
![]() | 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 / ![]() ![]() |
PubMed 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 ...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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Methods | EM (single particle) |
Resolution | 9.9 - 10.2 Å |
Structure data | ![]() EMDB-42400: RORC mRNA 3'UTR riboswitch A97G/G98A mutant class C ![]() EMDB-42401: RORC mRNA 3'UTR riboswitch 77-GA mutant class A ![]() EMDB-42403: RORC mRNA 3'UTR riboswitch 117-AC mutant class C ![]() EMDB-42404: RORC mRNA 3'UTR riboswitch 117-AC mutant class B |
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