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- A systematic search for RNA structural switches across the human transcriptome
A systematic search for RNA structural switches across the human transcriptome
Authors
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
Abstract
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 3ʹ 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