| First Author | Havens MA | Year | 2012 |
| Journal | Nucleic Acids Res | Volume | 40 |
| Issue | 10 | Pages | 4626-40 |
| PubMed ID | 22270084 | Mgi Jnum | J:197722 |
| Mgi Id | MGI:5494376 | Doi | 10.1093/nar/gks026 |
| Citation | Havens MA, et al. (2012) Biogenesis of mammalian microRNAs by a non-canonical processing pathway. Nucleic Acids Res 40(10):4626-40 |
| abstractText | Canonical microRNA biogenesis requires the Microprocessor components, Drosha and DGCR8, to generate precursor-miRNA, and Dicer to form mature miRNA. The Microprocessor is not required for processing of some miRNAs, including mirtrons, in which spliceosome-excised introns are direct Dicer substrates. In this study, we examine the processing of putative human mirtrons and demonstrate that although some are splicing-dependent, as expected, the predicted mirtrons, miR-1225 and miR-1228, are produced in the absence of splicing. Remarkably, knockout cell lines and knockdown experiments demonstrated that biogenesis of these splicing-independent mirtron-like miRNAs, termed 'simtrons', does not require the canonical miRNA biogenesis components, DGCR8, Dicer, Exportin-5 or Argonaute 2. However, simtron biogenesis was reduced by expression of a dominant negative form of Drosha. Simtrons are bound by Drosha and processed in vitro in a Drosha-dependent manner. Both simtrons and mirtrons function in silencing of target transcripts and are found in the RISC complex as demonstrated by their interaction with Argonaute proteins. These findings reveal a non-canonical miRNA biogenesis pathway that can produce functional regulatory RNAs. |
