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mRNA structure dynamics identifies the embryonic RNA regulome

Jean-Denis Beaudoin, Eva Maria Novoa, Charles E Vejnar, Valeria Yartseva, Carter Takacs, Manolis Kellis, Antonio J Giraldez
doi: https://doi.org/10.1101/274290
Jean-Denis Beaudoin
1Department of Genetics, Yale University School of Medicine, New Haven, Connecticut 06510, USA
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  • For correspondence: antonio.giraldez@yale.edu Jean-Denis.Beaudoin@yale.edu
Eva Maria Novoa
2Computer Science and Electrical Engineering Department, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA
3The Broad Institute of MIT and Harvard, Cambridge, Massachusetts 02139 USA
4Department of Neuroscience; Garvan Institute of Medical Research Darlinghurst NSW 2010 Australia
5School of Medicine, University of New South Wales, Sydney NSW 2052 Australia
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Charles E Vejnar
1Department of Genetics, Yale University School of Medicine, New Haven, Connecticut 06510, USA
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Valeria Yartseva
1Department of Genetics, Yale University School of Medicine, New Haven, Connecticut 06510, USA
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Carter Takacs
1Department of Genetics, Yale University School of Medicine, New Haven, Connecticut 06510, USA
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Manolis Kellis
2Computer Science and Electrical Engineering Department, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA
3The Broad Institute of MIT and Harvard, Cambridge, Massachusetts 02139 USA
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Antonio J Giraldez
1Department of Genetics, Yale University School of Medicine, New Haven, Connecticut 06510, USA
6Yale Stem Cell Center, Yale University School of Medicine, New Haven, Connecticut 06520 USA
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  • For correspondence: antonio.giraldez@yale.edu Jean-Denis.Beaudoin@yale.edu
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Abstract

RNA folding plays a crucial role in RNA function. However, our knowledge of the global structure of the transcriptome is limited to steady-state conditions, hindering our understanding of how RNA structure dynamics influences gene function. Here, we have characterized mRNA structure dynamics during zebrafish development. We observe that on a global level, translation guides structure rather than structure guiding translation. We detect a decrease in structure in translated regions, and we identify the ribosome as a major remodeler of RNA structure in vivo. In contrast, we find that 3’-UTRs form highly folded structures in vivo, which can affect gene expression by modulating miRNA activity. Furthermore, we find that dynamic 3’-UTR structures encode RNA decay elements, including regulatory elements in nanog and cyclin A1, key maternal factors orchestrating the maternal-to-zygotic transition. These results reveal a central role of RNA structure dynamics in gene regulatory programs.

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Posted March 01, 2018.
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mRNA structure dynamics identifies the embryonic RNA regulome
Jean-Denis Beaudoin, Eva Maria Novoa, Charles E Vejnar, Valeria Yartseva, Carter Takacs, Manolis Kellis, Antonio J Giraldez
bioRxiv 274290; doi: https://doi.org/10.1101/274290
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mRNA structure dynamics identifies the embryonic RNA regulome
Jean-Denis Beaudoin, Eva Maria Novoa, Charles E Vejnar, Valeria Yartseva, Carter Takacs, Manolis Kellis, Antonio J Giraldez
bioRxiv 274290; doi: https://doi.org/10.1101/274290

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