RNA polymerase III transcribes human microRNAs

Abstract

Prior work demonstrates that mammalian microRNA (miRNA or miR) expression requires RNA polymerase II (Pol II). However, the transcriptional requirements of many miRNAs remain untested. Our genomic analysis of miRNAs in the human chromosome 19 miRNA cluster (C19MC) revealed that they are interspersed among Alu repeats. Because Alu transcription occurs through RNA Pol III recruitment, and we found that Alu elements upstream of C19MC miRNAs retain sequences important for Pol III activity, we tested the promoter requirements of C19MC miRNAs. Chromatin immunoprecipitation and cell-free transcription assays showed that Pol III, but not Pol II, is associated with miRNA genomic sequence and sufficient for transcription. Moreover, the mature miRNA sequences of approximately 50 additional human miRNAs lie within Alu and other known repetitive elements. These findings extend the current view of miRNA origins and the transcriptional machinery driving their expression.

HepatomiRNoma: The proposal of a new network of targets for diagnosis, prognosis and therapy in hepatocellular carcinoma

“…MiRNA biogenesis is a multistep process that begins in the nucleus where the RNA polymerase II or RNA polymerase III, after binding to the promoter, transcribes a long primary transcript called pri-miRNA, an inactive form about 1 Kb in length (Lee et al, 2004;Borchert et al, 2006). The pri-miRNA is then processed by the Microprocessor complex consisting of Drosha, an RNase III endonuclease, its partner DGCR8 and associated proteins, into approximately 70-nucleotide incomplete, hairpin-like miRNA precursor (pre-miRNA) (Gregory et al, 2004).…”

Molecular medicine of microRNAs: structure, function and implications for diabetes

“…23), and bioinformatic analysis suggests that miRNA sequences containing upstream Alu, tRNA and mammalian-wide interspersed repeat (MWIR) sequences may also be transcribed by RNA pol III (Ref. 23). These transcripts are subsequently capped, polyadenylated and spliced, generating primary miRNA transcripts (pri-miRNAs) (Ref.…”

Regulation of mammalian gene expression by retroelements and non‐coding tandem repeats

“…This is likely in view of the growing evidence for the roles of transcripts from non-coding DNAs in eukaryotes. (23,36) Exchange of GFP-HP1 in heterochromatin is also inhibited by ActD but is stimulated by alpha-amanitin. (97) In interphase nuclei, ITS do not colocalize with transcription foci (''hubs'') detected by analysis of incorporation of 5-bromouridine monophosphate into RNA in vivo (96) indicating that ITS are not associated with extensively transcribed genome compartments.…”

“…(34) Nevertheless, the major human SINE1 (Alu elements) are poorly transcribed by RNA polymerase III in vivo. (35) Some Alu can bind TFIIIC and initiate RNA polymerase III-dependent transcription of microRNA genes in vivo (36) but it remains uncertain what fraction of all genomic SINEs actually bind TFIIIC in the nucleus. Many SINEs have a mutated B-box and cannot be transcribed by RNA polymerase III.…”