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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.

SUBMITTER: Chaulk SG 

PROVIDER: S-EPMC4005684 | biostudies-literature | 2014 Apr

REPOSITORIES: biostudies-literature

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MicroRNA miR-92a-1 biogenesis and mRNA targeting is modulated by a tertiary contact within the miR-17~92 microRNA cluster.

Chaulk Steven G SG   Xu Zhizhong Z   Glover Mark J N MJ   Fahlman Richard P RP  

Nucleic acids research 20140211 8


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  ...[more]

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