Implication of MicroRNAs in the Pathophysiology of Cardiac and Vascular Smooth Muscle Cells (original) (raw)

Current Basic and Pathological Approaches to the Function of Muscle Cells and Tissues - From Molecules to Humans, 2012

Abstract

ABSTRACT In the last 10 years, microRNAs (miRNAs) have emerged as critical regulators of numerous physiological and pathological mechanisms [1-2], including cardiac and vascular smooth muscle cell (VSMC) plasticity [3-5]. These small molecules (approx. 20 to 25 nucleotides) comprise a novel and abundant class of endogenous interfering RNAs. More than 1 500 miRNAs are now listed by dedicated internet databases such as miRBase, Tarbase, MicroRNA.org or miRdb (See sub-chapter II for URL adresses). They are transcribed and matured, in a process known as miRNA biogenesis [6] which starts with the transcription of a larger RNA product, called pri-miRNA, by the RNA polymerase II in the vast majority of cases. Pri-miRNA, which is a few hundred to a few thousand nucleotides long, is then submitted to cleavage in the nucleus by a specific RNase III (Drosha) and its protein partner, DiGeorge syndrome critical region 8 (DGCR8), near the base of the miRNA hairpin stem. This process releases a pre-miRNA hairpin (of approx. 60 to 70 nt). The pre-miRNA is then released in the cytoplasm where it is recognized and cleaved within its stems by the Dicer RNase III and its protein partners. This results in a double stranded RNA, known as the miRNA/miRNA* duplex (approx. 22 bp). This complex is unwound to single strands. One strand (guiding strand / mature miRNA) is incorporated in the RNA-induced-silencing complex (RISC) that contains Argonaute 2 (Ago2), another endonuclease, the other strand is usually rapidly degraded. Finally, the RISC complex carries the mature miRNA to its target messenger RNAs (mRNAs), which results in gene silencing, in a post-transcriptional manner [7]. Figure 1 shows a representative example of the biogenesis of miR-143 and miR-145, which are the main miRNAs expressed in smooth muscle cells.

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