Profiling of N⁶-methyladenosine dynamics indicates regulation of oyster development by m⁶A-RNA epitranscriptomes

Abstract

The N⁶-methylation of RNA adenosines (m⁶A) is an important regulator of gene expression with critical implications in vertebrate and insect development. However, the developmental significance of epitranscriptomes in lophotrochozoan organisms remains unknown.

Using MeRIP-seq, we generated transcriptome-wide m⁶A-RNA methylomes covering the whole development of the oyster from oocytes to juveniles. Oyster RNA classes display specific m⁶A signatures, with mRNAs and lncRNAs exhibiting distinct profiles and being highly methylated compared to transposon transcripts. Epitranscriptomes are dynamic and correspond to chronological steps of development (cleavage, gastrulation, organogenesis and metamorphosis), with a minimal mRNA and lncRNA methylation at the morula stage followed by a global increase. mRNA m⁶A levels are correlated to transcript levels and shifts in methyladenine profiles correspond to expression kinetics. Differentially methylated transcripts cluster according to embryo-larval stages and bear the corresponding developmental functions (cell division, signal transduction, morphogenesis and cell differentiation). The m⁶A level of transposon transcripts is also regulated and peaks during the gastrulation.

We demonstrate that m⁶A-RNA methylomes are dynamic and associated to gene expression regulation during oyster development. The putative epitranscriptome implication in the cleavage, maternal-to-zygotic transition and cell differentiation in a lophotrochozoan model brings new insights into the control and evolution of developmental processes