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You are here: Home / Teams / Regulation of Genome Architecture and Dynamics of Splicing (ReGArDS) - D. Auboeuf and C. Bourgeois / Publications / RNA helicase-dependent gene looping impacts messenger RNA processing.

RNA helicase-dependent gene looping impacts messenger RNA processing.

Sophie Terrone, Jessica Valat, Nicolas Fontrodona, Guillaume Giraud, Jean-Baptiste Claude, Emmanuel Combe, Audrey Lapendry, Hélène Polvèche, Lamya B Ameur, Arnaud Duvermy, Laurent Modolo, Pascal Bernard, Franck Mortreux, Didier Auboeuf, and Cyril F Bourgeois (2022)

Nucleic Acids Res, 50(16):9226-46.

DDX5 and DDX17 are DEAD-box RNA helicase paralogs which regulate several aspectsof gene expression, especially transcription and splicing, through incompletelyunderstood mechanisms. A transcriptome analysis of DDX5/DDX17-depleted humancells confirmed the large impact of these RNA helicases on splicing and revealeda widespread deregulation of 3' end processing. In silico analyses andexperiments in cultured cells showed the binding and functional contribution ofthe genome organizing factor CTCF to chromatin sites at or near a subset ofDDX5/DDX17-dependent exons that are characterized by a high GC content and a highdensity of RNA Polymerase II. We propose the existence of an RNAhelicase-dependent relationship between CTCF and the dynamics of transcriptionacross DNA and/or RNA structured regions, that contributes to the processing ofinternal and terminal exons. Moreover, local DDX5/DDX17-dependent chromatin loopsspatially connect RNA helicase-regulated exons with their cognate promoter, andwe provide the first direct evidence that de novo gene looping modifiesalternative splicing and polyadenylation. Overall our findings uncover the impactof DDX5/DDX17-dependent chromatin folding on pre-messenger RNA processing.

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