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Publication : The germ cell-specific RNA binding protein RBM46 is essential for spermatogonial differentiation in mice.

First Author  Peart NJ Year  2022
Journal  PLoS Genet Volume  18
Issue  9 Pages  e1010416
PubMed ID  36129965 Mgi Jnum  J:330079
Mgi Id  MGI:7345005 Doi  10.1371/journal.pgen.1010416
Citation  Peart NJ, et al. (2022) The germ cell-specific RNA binding protein RBM46 is essential for spermatogonial differentiation in mice. PLoS Genet 18(9):e1010416
abstractText  Control over gene expression is exerted, in multiple stages of spermatogenesis, at the post-transcriptional level by RNA binding proteins (RBPs). We identify here an essential role in mammalian spermatogenesis and male fertility for 'RNA binding protein 46' (RBM46). A highly evolutionarily conserved gene, Rbm46 is also essential for fertility in both flies and fish. We found Rbm46 expression was restricted to the mouse germline, detectable in males in the cytoplasm of premeiotic spermatogonia and meiotic spermatocytes. To define its requirement for spermatogenesis, we generated Rbm46 knockout (KO, Rbm46-/-) mice; although male Rbm46-/- mice were viable and appeared grossly normal, they were infertile. Testes from adult Rbm46-/- mice were small, with seminiferous tubules containing only Sertoli cells and few undifferentiated spermatogonia. Using genome-wide unbiased high throughput assays RNA-seq and 'enhanced crosslinking immunoprecipitation' coupled with RNA-seq (eCLIP-seq), we discovered RBM46 could bind, via a U-rich conserved consensus sequence, to a cohort of mRNAs encoding proteins required for completion of differentiation and subsequent meiotic initiation. In summary, our studies support an essential role for RBM46 in regulating target mRNAs during spermatogonia differentiation prior to the commitment to meiosis in mice.
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