RBM46 promotes meiotic initiation during oogenesis

RNA binding protein RBM46, as an integral component of MEIOC-YTHDC2 complex, governs the RNA binding specificity in posttranscriptional regulation of male meiotic initiation. RBM46 is also indispensable for embryonic oocyte development in mice. However, the precise phenotypic consequences and underlying regulatory mechanisms of RBM46 in female germ cells remain largely uncharacterized. Here, we demonstrate that RBM46 deficiency leads to derepression of CCNA2, meiotic arrest at leptotene stage and widespread germ cell apoptosis in embryonic ovaries. Transcriptomic profiling of RBM46-deficient ovaries at embryonic day 16.5 revealed significant upregulation of Stra8 and Lin28a, alongside downregulation of multiple meiotic genes. In HEK293T cells, ectopic co-expression of RBM46, MEIOC and YTHDC2 promoted degradation of reporter mRNAs bearing either Lin28a or Mga 3'UTR. Notably, Deletion of the RBM46-binding motif "AAUCAU" within Lin28a 3'UTR reduced this repressive effect. Collectively, these findings establish an essential role of RBM46 for meiotic initiation in female germ cells and identify Lin28a and Mga transcripts as direct targets subject to RBM46-mediated decay.