Pluto Bioinformatics

GSE95138: An orchestrated intron retention program in meiosis controls timely usage of transcripts during germ cell differentiation (RNA-Seq)

Bulk RNA sequencing

Alternative splicing (AS) represents a powerful resource to amplify the coding potential of eukaryotic genomes and to finely tune gene expression during cell differentiation and development. Notably, high-throughput transcriptome analyses identified testis among the tissues displaying the highest proportion of AS events and profiling of whole testis transcriptome during the first wave of mouse spermatogenesis highlighted some AS events that are timely regulated during this process. Thus, AS modulation likely contributes to the fine-tuned regulation of gene expression that occurs during the male germ cell differentiation. In particular, meiotic spermatocytes and post-meiotic spermatids are known to express a highly specific repertoire of protein variants. However, no study has directly investigated whether global splicing-changes occur during the trans-meiotic phases of spermatogenesis to date. Spermatocytes undergo two consecutive meiotic divisions to yield haploid post-meiotic spermatids, which then differentiate into highly specialized and motile spermatozoa. Herein, to achieve a comprehensive characterization of the splicing changes occurring during trans-meiotic differentiation of male germ cells, we performed high-throughput RNA sequencing (RNA-seq) analyses of polyA+ RNA isolated from highly purified populations of meiotic spermatocytes and post-meiotic spermatids. Our analysis uncovered a robust intron retention (IR) program in meiotic spermatocytes. Intron-retaining genes were strongly enriched in functional categories related to differentiation and properties of the male gamete. We found that meiotic intron-retaining transcripts are long-lived mRNAs, which are preserved in the nucleus until they need to be translated. Thus, our study reveals an unexpected physiological role for IR in ensuring proper and timely control of gene expression during male germ cell differentiation. SOURCE: Pierre de la Grange (pierre.delagrange@genosplice.com) - GenoSplice technology