MicroRNA: Biogenesis, Function and Role in Cancer

By Leigh-Ann MacFarlane, P. Murphy. Current Genomics, 2010

1,721 citations recorded by the source corpus.

MicroRNAs are small, highly conserved non-coding RNA molecules involved in the regulation of gene expression. MicroRNAs are transcribed by RNA polymerases II and III, generating precursors that undergo a series of cleavage events to form mature microRNA. The conventional biogenesis pathway consists of two cleavage events, one nuclear and one cytoplasmic. However, alternative biogenesis pathways exist that differ in the number of cleavage events and enzymes responsible. How microRNA precursors are sorted to the different pathways is unclear but appears to be determined by the site of origin of the microRNA, its sequence and thermodynamic stability. The regulatory functions of microRNAs are accomplished through the RNA-induced silencing complex (RISC). MicroRNA assembles into RISC, activating the complex to target messenger RNA (mRNA) specified by the microRNA. Various RISC assembly models have been proposed and research continues to explore the mechanism(s) of RISC loading and activation. The degree and nature of the complementarity between the microRNA and target determine the gene silencing mechanism, slicer-dependent mRNA degradation or slicer-independent translation inhibition. Recent evidence indicates that P-bodies are essential for microRNA-mediated gene silencing and that RISC assembly and silencing occurs primarily within P-bodies. The P-body model outlines microRNA sorting and shuttling between specialized P-body compartments that house enzymes required for slicer –dependent and –independent silencing, addressing the reversibility of these silencing mechanisms. Detailed knowledge of the microRNA pathways is essential for understanding their physiological role and the implications associated with dysfunction and dysregulation.

Subfields: Cancer Research, Molecular Biology

View Paper: https://www.semanticscholar.org/paper/b6f98dbf0d813d9fbb8271bd5e58b31ab1cb29ef

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Citations in the corpus

Molecular mechanisms of RNA interference (2013, neutral): “Eventually such miRNAs were found to be widespread: As much as 5% of the human genome is dedicated to encoding and producing the >1,000 miRNAs that regulate at least 30% of our genes (38, 58).”
PARP Inhibitors: Clinical Relevance, Mechanisms of Action and Tumor Resistance (2020, background): “microRNAs are small, highly conserved regions of non-coding RNA, recognized to have a role in regulating gene expression (Macfarlane and Murphy, 2010).”
In vivo delivery of miRNAs for cancer therapy: Challenges and strategies (2014, background): “RISC is a key enzyme that facilitates the mature miRNAs interacting with complementary 3′ UTRs of target mRNAs, enabling miRNAs to regulate the target gene expression [23].”