One locus with two roles: microRNA‐independent functions of microRNA‐host‐gene locus‐encoded long noncoding RNAs

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Qinyu Sun, You Jin Song, Kannanganattu V. Prasanth

Published Online: Sep 17 2020

DOI: 10.1002/wrna.1625

Full article on Wiley Online Library: HTML PDF

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Abstract Long noncoding RNAs (lncRNAs) are RNA transcripts longer than 200 nucleotides that do not code for proteins. LncRNAs play crucial regulatory roles in several biological processes via diverse mechanisms and their aberrant expression is associated with various diseases. LncRNA genes are further subcategorized based on their relative organization in the genome. MicroRNA (miRNA)‐host‐gene‐derived lncRNAs (lnc‐MIRHGs) refer to lncRNAs whose genes also harbor miRNAs. There exists crosstalk between the processing of lnc‐MIRHGs and the biogenesis of the encoded miRNAs. Although the functions of the encoded miRNAs are usually well understood, whether those lnc‐MIRHGs play independent functions are not fully elucidated. Here, we review our current understanding of lnc‐MIRHGs, including their biogenesis, function, and mechanism of action, with a focus on discussing the miRNA‐independent functions of lnc‐MIRHGs, including their involvement in cancer. Our current understanding of lnc‐MIRHGs strongly indicates that this class of lncRNAs could play important roles in basic cellular events as well as in diseases. This article is categorized under: Regulatory RNAs/RNAi/Riboswitches > Regulatory RNAs Regulatory RNAs/RNAi/Riboswitches > Biogenesis of Effector Small RNAs

Categorization of miRNAs with respect to their relationship with miRNA‐host‐genes (MIRHGs)

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Summary of lnc‐MIRHG loci outcome. (a) Only generates miRNA; the lnc‐MIRHG nascent transcript degrades quickly. (b) The loci only produces one type of ncRNA: either miRNA or lnc‐MIRHG can be generated. (c) The loci can produce both miRNA and lnc‐MIRHG. (d) The loci exerts low miRNA production efficiency and only produces lnc‐MIRHG (NEAT1 example)

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Molecular mechanisms of lnc‐MIRHGs. (a) ceRNA. (b) Interacting with DNA elements. (c) Interacting with proteins. (ca) Regulating the interacting protein(s). Top: stabilizing the interacting protein. Bottom: mediating protein–protein interaction. (cb) Recruiting/titrating protein factors to regulate transcription. (cc) Recruiting/titrating protein factors to regulate post‐transcriptional regulation. (cd) Global regulation of primary RNA processing (NEAT1). (ce) Maintaining nuclear structure (NEAT1).(d) Peptide encoding. Example is the circular LINC‐PINT

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Different models of MIRHG splicing and intragenic miRNA biogenesis. (a–c) Synergetic model. (a) Mirtron. (b) Splicing machinery and microprocessors facilitate each other. (c) Splicing factors facilitate miRNA production in a splicing‐independent manner. (d,e) Competition model. (d) Alternative‐splicing‐mediated miRNA production. Two scenarios of alternative splicing are depicted. (e) Nonalternative‐splicing‐mediated miRNA production

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