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Nat Struct Mol Biol. 2018 Aug;25(8):677-686. doi: 10.1038/s41594-018-0091-z. Epub 2018 Jul 30.

Analyses of mRNA structure dynamics identify embryonic gene regulatory programs.

Author information

1
Department of Genetics, Yale University School of Medicine, New Haven, CT, USA. jean-denis.beaudoin@yale.edu.
2
Computer Science and Electrical Engineering Department, Massachusetts Institute of Technology, Cambridge, MA, USA.
3
The Broad Institute of MIT and Harvard, Cambridge, MA, USA.
4
Department of Neuroscience, Garvan Institute of Medical Research, Darlinghurst, New South Wales, Australia.
5
School of Medicine, University of New South Wales, Sydney, New South Wales, Australia.
6
Department of Genetics, Yale University School of Medicine, New Haven, CT, USA.
7
College of Arts and Sciences, University of New Haven, West Haven, CT, USA.
8
Department of Genetics, Yale University School of Medicine, New Haven, CT, USA. antonio.giraldez@yale.edu.
9
Yale Stem Cell Center, Yale University School of Medicine, New Haven, CT, USA. antonio.giraldez@yale.edu.

Abstract

RNA folding plays a crucial role in RNA function. However, knowledge of the global structure of the transcriptome is limited to cellular systems at steady state, thus hindering the understanding of RNA structure dynamics during biological transitions and how it influences gene function. Here, we characterized mRNA structure dynamics during zebrafish development. We observed that on a global level, translation guides structure rather than structure guiding translation. We detected a decrease in structure in translated regions and identified the ribosome as a major remodeler of RNA structure in vivo. In contrast, we found that 3' untranslated regions (UTRs) form highly folded structures in vivo, which can affect gene expression by modulating microRNA activity. Furthermore, dynamic 3'-UTR structures contain RNA-decay elements, such as the regulatory elements in nanog and ccna1, two genes encoding key maternal factors orchestrating the maternal-to-zygotic transition. These results reveal a central role of RNA structure dynamics in gene regulatory programs.

PMID:
30061596
DOI:
10.1038/s41594-018-0091-z

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