N6-methyladenosine dynamics during early vertebrate embryogenesis
Håvard AanesiD, Dominique Engelsen, Adeel ManafiD, Endalkachew Ashenafi Alemu, Cathrine Broberg VågbøiD, Leonardo MartíniD, Mads LerdrupiD, Klaus H. HanseniD, Sinnakaruppan MathavaniD, Cecilia Lanny WinataiD, Robert B. DarnelliD, Peter AleströmiD, Arne KlunglandiD
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 3UTR, 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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