title: MicroRNA miR-92a-1 biogenesis and mRNA targeting is modulated by a tertiary contact within the miR-17~92 microRNA cluster.
abstract: While functional mature microRNAs (miRNAs) are small ∼22 base oligonucleotides that target specific mRNAs, miRNAs are initially expressed as long transcripts (pri-miRNAs) that undergo sequential processing to yield the mature miRNAs. We have previously reported that the pri-miR-17∼92 cluster adopts a compact globular folded structure that internalizes a 3' core domain resulting in reduced miRNA maturation and subsequent mRNA targeting. Using a site-specific photo-cross-linker we have identified a tertiary contact within the 3' core domain of the pri-miRNA between a non-miRNA stem-loop and the pre-miR-19b hairpin. This tertiary contact is involved in the formation of the compact globular fold of the cluster while its disruption enhances miR-92a expression and mRNA targeting. We propose that this tertiary contact serves as a molecular scaffold to restrict expression of the proposed antiangiogenic miR-92a, allowing for the overall pro-angiogenic effect of miR-17∼92 expression.
authors: Department of Biochemistry, University of Alberta, Edmonton, Alberta T6G 2H7, Canada and Department of Oncology, University of Alberta, Edmonton, Alberta T6G 2H7, Canada.
authors: Steven G
authors: SG
authors: Chaulk
authors: Zhizhong
authors: Z
authors: Xu
authors: Mark J N
authors: MJ
authors: Glover
authors: Richard P
authors: RP
authors: Fahlman
mesh_terms: D000241:Adenosine / Q000032:analysis; D020029:Base Pairing; D057809:HEK293 Cells; D006367:HeLa Cells; D006801:Humans; D035683:MicroRNAs / Q000737:chemistry* / Q000378:metabolism*; D009690:Nucleic Acid Conformation; D059370:RNA Folding; D012322:RNA Precursors / Q000737:chemistry; D062085:RNA, Long Noncoding; D012333:RNA, Messenger / Q000378:metabolism*; D012091:Repetitive Sequences, Nucleic Acid; D043244:Ribonuclease III / Q000378:metabolism
chemical_list: C568997:MIR17HG, human; C549214:MIRN19A microRNA, human; C541874:MIRN92 microRNA, human; D035683:MicroRNAs; D012322:RNA Precursors; D062085:RNA, Long Noncoding; D012333:RNA, Messenger; C517918:DROSHA protein, human; D043244:Ribonuclease III; D000241:Adenosine