m6A Profile Dynamics Indicates Regulation of Oyster Development by m6A-RNA Epitranscriptomes

The N-6-methylation of RNA adenosines (N-6-methyladenosine, m(6)A) 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 methylated RNA immunoprecipitation sequencing (MeRIP-seq), we generated transcriptome-wide m(6)A-RNA methylomes covering the entire development of the oyster from oocytes to juveniles. Oyster RNA classes display specific m(6)A signatures, with messenger RNAs (mRNAs) and long non-coding RNAs (lncRNAs) exhibiting distinct profiles and being highly methylated compared to transposable element (TE) transcripts. Epitranscriptomes are dynamic and correspond to the chronological steps of development (cleavage, gastrulation, organogenesis, and <bold>metamorphosis</bold>), with minimal mRNA and lncRNA methylation at the morula stage followed by a global increase. mRNA m(6)A levels are correlated with transcript levels, and shifts in methylation profiles correspond to expression kinetics. Differentially methylated transcripts cluster according to <bold>embryo</bold>-larval stages and bear the corresponding developmental functions (cell division, signal transduction, morphogenesis, and cell differentiation). The m(6)A level of TE transcripts is also regulated and peaks during the gastrulation. We demonstrate that m(6)A-RNA methylomes are dynamic and associated with 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.