Abstract
MicroRNAs (miRNAs) are important posttranscriptional regulators of gene expression. However, comprehensive expression profiles of miRNAs during mammalian spermatogenesis are lacking. Herein, we sequenced small RNAs in highly purified mouse spermatogenic cells at different stages. We found that a family of X-linked miRNAs named spermatogenesis-related miRNAs (spermiRs) is predominantly expressed in the early meiotic phases and has a conserved testis-specific high expression pattern in different mammals. We identified one spermiR homolog in opossum; this homolog might originate from THER1, a retrotransposon that is active in marsupials but extinct in current placental mammals. SpermiRs have expanded rapidly with mammalian evolution and are diverged into two clades, spermiR-L and spermiR-R, which are likely to have been generated at least in part by tandem duplication mediated by flanking retrotransposable elements. Notably, despite having undergone highly frequent lineage-specific duplication events, the sequences encoding all spermiR family members are strictly located between two protein-coding genes, Slitrk2 and Fmr1. Moreover, spermiR-Ls and spermiR-Rs have evolved different expression patterns during spermatogenesis in different mammals. Intriguingly, the seed sequences of spermiRs, which are critical for the recognition of target genes, are highly divergent within and among mammals, whereas spermiR target genes largely overlap. When miR-741, the most highly expressed spermiR, is knocked out in cultured mouse spermatogonial stem cells (SSCs), another spermiR, miR-465a-5p, is dramatically upregulated and becomes the most abundant miRNA. Notably, miR-741−/− SSCs grow normally, and the genome-wide expression levels of mRNAs remain unchanged. All these observations indicate functional compensation between spermiR family members and strong coevolution between spermiRs and their targets.
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