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N6-methyladenosine dynamics during early vertebrate embryogenesis

Havard Aanes, Dominique Engelsen, Adeel Manaf, Endalkachew Ashenafi Alemu, Cathrine Broberg Vagbo, Leonardo Martin, Mads Lerdrup, Klaus Hansen, Sinnakaruppan Mathavan, Cecilia Winata, Robert B. Darnell, Peter Alestrom, Arne Klungland
doi: https://doi.org/10.1101/528422
Havard Aanes
Oslo University Hospital;
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  • For correspondence: havard.aanes@rr-research.no
Dominique Engelsen
Oslo University Hospital;
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Adeel Manaf
Oslo University Hospital;
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Endalkachew Ashenafi Alemu
Oslo University Hospital;
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Cathrine Broberg Vagbo
Norwegian University of Science and Technology;
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Leonardo Martin
Norwegian School of Veterinary Science;
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Mads Lerdrup
University of Copenhagen;
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Klaus Hansen
University of Copenhagen;
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Sinnakaruppan Mathavan
Genome Institute of Singapore;
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Cecilia Winata
International Institute of Molecular and Cell Biology;
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Robert B. Darnell
The Rockefeller University
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Peter Alestrom
Norwegian School of Veterinary Science;
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Arne Klungland
Oslo University Hospital;
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Abstract

Early vertebrate embryogenesis is characterized by extensive post-transcriptional regulation during the maternal-to-zygotic transition. The N6-methyladenosine (m6A) modifications on mRNA have been shown to affect both translation and stability of transcripts. Here we investigate the m6A topology during early vertebrate embryogenesis and its association with polyadenylated mRNA levels. The majority (>70%) of maternal transcripts harbor m6A, and there is a substantial increase of m6A in the polyadenylated mRNA fraction between 0 and 2 hours post fertilization. Notably, we find strong associations between m6A, cytoplasmic polyadenylation and translational efficiency prior to zygotic genome activation (ZGA). Interestingly, the relationship between m6A and translation is strongest for peaks located in the 3 UTR, but not overlapping stop codons. Sequence analyses revealed enrichment of motifs for RNA binding proteins involved in translational regulation and RNA degradation. After ZGA, m6A seem to diminish the effect of miR-430 mediated degradation. The reported results improve our understanding of the combinatorial code behind post-transcriptional mRNA regulation during embryonic reprogramming and early differentiation.

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Posted January 23, 2019.
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N6-methyladenosine dynamics during early vertebrate embryogenesis
Havard Aanes, Dominique Engelsen, Adeel Manaf, Endalkachew Ashenafi Alemu, Cathrine Broberg Vagbo, Leonardo Martin, Mads Lerdrup, Klaus Hansen, Sinnakaruppan Mathavan, Cecilia Winata, Robert B. Darnell, Peter Alestrom, Arne Klungland
bioRxiv 528422; doi: https://doi.org/10.1101/528422
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N6-methyladenosine dynamics during early vertebrate embryogenesis
Havard Aanes, Dominique Engelsen, Adeel Manaf, Endalkachew Ashenafi Alemu, Cathrine Broberg Vagbo, Leonardo Martin, Mads Lerdrup, Klaus Hansen, Sinnakaruppan Mathavan, Cecilia Winata, Robert B. Darnell, Peter Alestrom, Arne Klungland
bioRxiv 528422; doi: https://doi.org/10.1101/528422

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