microRNA processing by splicing

Posted by Hamed Shateri Najafabadi

My colleage, Yuan, sent me a paper a while ago that had interesting points on possible mechanisms of microRNA processing. Ruby, Jan and Bartel from MIT in their paper, “Intronic microRNA precursors that bypass Drosha processing” (Nature 2007, 448:83-86), report a new mechanism for maturation of microRNAs from introns. This Drosha-independent mechanism recruits the splicing machinery to produce pre-miRNAs/introns that the authors, tastefully, call ‘mirtrons’ (the conventional pathway requires the enzyme Drosha to cleave pri-miRNA transcripts into pre-miRNAs, see Figure below). This paper is a beautiful example of how high-throughput sequencing, spiced by open minds and sharp eyes can lead into spectacular findings. I would like to quote the last sentences of this paper: “This mechanism, together with that of mirtron processing, would enable miRNAs to emerge in any organism with both splicing and post-transcriptional RNA silencing, even those lacking the specialized RNase III enzyme Drosha or its plant counterpart, DICER-LIKE1. In this scenario, miRNAs might have emerged in ancient eukaryotes before the advent of modern miRNA biogenesis pathways.”

Model for convergence of the canonical and mirtronic miRNA biogenesis pathways