Multi-omic screening identifies RBMXL3 as a primate-specific RNA-binding protein and candidate regulator of RNA metabolism in human spermatogenesis

RBMXL3 is a primate-specific gene localized on the X chromosome, which expression is detectable mainly in the male gonad. So far, very little is known about the RBMXL3 protein function and its molecular interactions. Still, recent reports mention the RBMXL3 gene in the context of human spermatogenesis, cancer, and a breathing disorder that affects newborns. In this study, we investigate the RBMXL3's molecular network on a genome-wide scale using the human seminoma cell line (TCam-2) as a male germline in vitro model. By using transcriptomic (RNAseq, eCLIP) and proteomic (Co-IP coupled with MS) approaches we show RBMXL3 importance in RNA metabolism. Moreover, we report for the first time that primate-specific RBMXL3 protein restricts human LINE-1 (L1) retrotransposition. Our data suggest that RBMXL3 may contribute to the regulation of transcriptome dynamics in germ cells, while its broader functional implications remain to be determined.