Transcriptome profiling of the developing male germ line identifies the miR-29 family as a global regulator during meiosis.

MicroRNAs are essential for spermatogenesis. However, the stage-specific requirements for particular miRNAs in the male mammalian germ line remain largely uncharacterized. The miR-34 family is, to date, the only miRNA proven to be necessary for the production of sperm in mammals, though its germline roles are poorly understood. Here, we generate and analyze paired small RNA and mRNA profiles across different stages of germline development in male mice, focusing on time points shortly before and during meiotic prophase I. We show that in addition to miR-34, miR-29 also mediates widespread repression of mRNA targets during meiotic prophase I in the male mouse germline. Furthermore, we demonstrate that predicted miR-29 target mRNAs in meiotic cells are largely distinct from those of miR-34, indicating that miR-29 performs a regulatory function independent of miR-34. Prior to this work, no germline role has been attributed to miR-29. To begin to understand roles for miR-29 in the germ line, we identify targets of miR-29 undergoing post transcriptional downregulation during meiotic prophase I, which likely correspond to the direct targets of miR-29. Interestingly, candidate direct targets of miR-29 are enriched in transcripts encoding extracellular matrix components. Our results implicate the miR-29 family as an important regulatory factor during male meiosis.