Epitranscriptomic Profiling Reveals N7-Methylguanosine Modification as a Novel Regulator in Recurrent Spontaneous Abortion

Notably, genes with altered m7G modification were mostly enriched in embryonic and systemic morphogenesis and development. Moreover, we found an increased expression of the m7G methyltransferase METTL1 in the RSA decidua. RNA sequencing (RNA-seq) further revealed a vastly changed transcriptome in the RSA decidua.

Conjoint analysis of MeRIP-seq and RNA-seq further showed that the methylation levels and expression levels of 48 genes changed simultaneously in the RSA decidua. Furthermore, we identified 7 RSA-related genes such as SOCS3, RASA1, FLT1, and JUNB were downregulated, while GNLY was up-regulated in RSA decidua. More importantly, METTL1 showed high-affinity binding to target mRNAs harboring altered m7G modification, indicating dysregulated RSA-genes may be driven by METTL1-mediated m7G modification.

These findings provide novel insight into the functional role of m7G modification in RSA pathogenesis.