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Updated: Jun 21, 2025

Detection of Alternative Splicing During Epithelial-Mesenchymal Transition

Detection of Alternative Splicing During Epithelial-Mesenchymal Transition

Published on: October 9, 2014

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

Matvei Khoroshkin^1,2,3,4, Daniel Asarnow^1,5, Shaopu Zhou^1,2,3,4

¹Department of Biochemistry and Biophysics, University of California, San Francisco, San Francisco, CA, USA.

|July 16, 2024

Summary

This summary is machine-generated.

SwitchSeeker identifies novel RNA structural switches in humans, revealing their role in gene regulation. This method uses computational and experimental techniques to uncover these critical elements and their impact on gene expression.

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Area of Science:

Molecular Biology
Genomics
Bioinformatics

Background:

RNA structural switches regulate gene expression in bacteria, but are poorly understood in Metazoa.
Systematic identification of functional RNA structural switches in eukaryotes is lacking.

Purpose of the Study:

To develop and validate a comprehensive computational and experimental approach, SwitchSeeker, for identifying functional RNA structural switches in the human transcriptome.
To characterize a novel RNA structural switch in the RORC transcript and investigate its regulatory mechanisms.

Main Methods:

Application of SwitchSeeker to the human transcriptome for identification of putative RNA switches.
In vivo dimethyl sulfate mutational profiling with sequencing (DMS-MaPseq) and cryogenic electron microscopy for structural validation.
Genome-scale CRISPR screens to identify trans-acting factors regulating RNA structural switches.

Main Results:

Identification of 245 putative RNA structural switches in the human transcriptome.
Characterization of a novel switch in the RORC 3' untranslated region, existing in two alternative conformations.
Discovery that nonsense-mediated messenger RNA decay regulates this switch in a conformation-specific manner.

Conclusions:

SwitchSeeker is an effective, unbiased, and experimentally driven method for discovering RNA structural switches in eukaryotes.
RNA structural switches play a significant role in shaping the eukaryotic gene expression landscape.
Conformation-specific regulation by trans factors, including nonsense-mediated messenger RNA decay, highlights the complexity of RNA-based gene control.