Processing of intronic microRNAs

YK Kim, VN Kim - The EMBO journal, 2007 - embopress.org
YK Kim, VN Kim
The EMBO journal, 2007embopress.org
The majority of human microRNA (miRNA) loci are located within intronic regions and are
transcribed by RNA polymerase II as part of their hosting transcription units. The primary
transcripts are cleaved by Drosha to release∼ 70 nt pre‐miRNAs that are subsequently
processed by Dicer to generate mature∼ 22 nt miRNAs. It is generally believed that intronic
miRNAs are released by Drosha from excised introns after the splicing reaction has
occurred. However, our database searches and experiments indicate that intronic miRNAs …
The majority of human microRNA (miRNA) loci are located within intronic regions and are transcribed by RNA polymerase II as part of their hosting transcription units. The primary transcripts are cleaved by Drosha to release ∼70 nt pre‐miRNAs that are subsequently processed by Dicer to generate mature ∼22 nt miRNAs. It is generally believed that intronic miRNAs are released by Drosha from excised introns after the splicing reaction has occurred. However, our database searches and experiments indicate that intronic miRNAs can be processed from unspliced intronic regions before splicing catalysis. Intriguingly, cleavage of an intron by Drosha does not significantly affect the production of mature mRNA, suggesting that a continuous intron may not be required for splicing and that the exons may be tethered to each other. Hence, Drosha may cleave intronic miRNAs between the splicing commitment step and the excision step, thereby ensuring both miRNA biogenesis and protein synthesis from a single primary transcript. Our study provides a novel example of eukaryotic gene organization and RNA‐processing control.
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