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miRNAs regulate expression and function of extracellular matrix molecules - PubMed

  • ️Tue Jan 01 2013

Review

miRNAs regulate expression and function of extracellular matrix molecules

Zina Jeyapalan Rutnam et al. Matrix Biol. 2013.

Abstract

MicroRNAs (miRNAs) are a family of small non-coding RNA molecules that are made up of 18-25 nucleotides that function in post-transcriptional gene regulation. The expression of miRNAs is highly conserved and essential in regulating many cellular processes including formation, maintenance and the remodelling of the extracellular matrix (ECM). In this review, we examine different ECM molecules and the miRNAs involved in regulating their abundance and how these changes influence cell phenotype. For example, miRNAs and their target messenger RNAs (mRNAs) are involved in cell adhesion, by regulating the synthesis and turnover of key ECM adhesion molecules and their receptors including cadherins, integrins and other non-integrin ECM receptors. Other miRNAs regulate the abundance of cytokines and growth factors which in turn stimulate cells to synthesize and secrete specialized ECMs. For example, miR-125a/b and miR-146a and their downstream target mRNAs influence the production of the epidermal growth factor family which has a significant impact on the nature of the ECM formed. miRNAs affect structural ECM proteins important in the assembly, composition and organization of the ECM. Proteins such as collagen, fibronectin, versican, and nephronectin are targeted by several miRNAs. miRNAs can also control the expression of proteins such as matrix metalloproteinases (MMPs) and tissue inhibitor of metalloproteinases (TIMPs), which are involved in ECM remodelling and are important for tissue development, cell motility and wound healing. It has become clear that many different miRNAs control the balance in ECM composition that determines normal tissue function and alterations in the expression of these miRNAs can lead to pathological consequences.

Copyright © 2012 International Society of Matrix Biology. Published by Elsevier B.V. All rights reserved.

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Figures

Fig. 1
Fig. 1

miRNA biogenesis pathway. miRNA genes are transcribed by RNA Pol II/III to make pri-miRNA. pri-miRNA is cleaved by Drosha complexed with DGCR8 to become pre-miRNA which is exported by Exportin-5 and RanGTP complex into the cytoplasm. Dicer and TRBP complex and process it to create the miRNA:miRNA* duplex. Ago2 and RNP separate the duplex to create the mature miRNA. The mature miRNA binds with miRISC and Ago2 to silence target mRNAs.

Fig. 2
Fig. 2

Modulation of miRNAs by the CD44 3′UTR. In the absence of the exogenous 3′UTR, miRNAs and RISC are able to bind to the 3′UTRs of CD44, FN, Col1a1 and CDC42 and inhibit mRNA translation (left side). The 3′UTR of CD44 is able to bind and antagonize endogenous miRNAs, effectively allowing for related mRNAs, FN, Col1a1 and CDC42, along with CD44 to be expressed (right side).

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