The m6A demethylase ALKBH5 controls trophoblast invasion at the maternal-fetal interface by regulating the stability of <i>CYR61</i> mRNA

Abstract

N 6 -Methyladenosine (m 6 A) is the most prevalent internal modification in mammalian mRNAs. Although m 6 A is important in many biological processes, its roles in the placenta are unclear. Methods: Levels of global mRNA m 6 A methylation and ALKBH5 expression in recurrent miscarriage (RM) patients were determined using quantitative reverse transcription-PCR (qRT-PCR), m 6 A RNA methylation quantification, and immunohistochemical methods. Using ALKBH5 overexpression and knockdown methods, we determined the role of ALKBH5 in trophoblast invasion at the maternal interface through trophoblasts and an extravillous explant culture experiments. Furthermore, the regulation of CYR61 by ALKBH5 was explored by RNA-sequencing coupled with methylated RNA immunoprecipitation.