Post-transcriptional regulation in spermatogenesis: all RNA pathways lead to healthy sperm

Multiple RNA pathways are required to produce functional sperm. Here, we review RNA post-transcriptional regulation during spermatogenesis with particular emphasis on the role of 3' end modifications. From early studies in the 1970s, it became clear that spermiogenesis transcripts could be stored for days only to be translated at advanced stages of spermatid differentiation. The transition between the translationally repressed and active states was observed to correlate with the shortening of the transcripts' poly(A) tail, establishing a link between RNA 3' end metabolism and male germ cell differentiation. Since then, numerous RNA metabolic pathways have been implicated not only in the progression through spermatogenesis, but also in the maintenance of genomic integrity. Recent studies have characterized the elusive 3' biogenesis of Piwi-interacting RNAs (piRNAs), identified a critical role for messenger RNA (mRNA) 3' uridylation in meiotic progression, established the mechanisms that destabilize transcripts with long 3' untranslated regions (3'UTRs) in post-mitotic cells, and defined the physiological relevance of RNA exonucleases and deadenylases in male germ cells. In this review, we discuss RNA processing in the male germline in the light of the most recent findings. A brief recollection of different RNA-processing events will aid future studies exploring post-transcriptional regulation in spermatogenesis.