How Do MicroRNAs Regulate Gene Expression?

Abstract

Several thousand human genes, amounting to about one-third of the whole genome, are potential targets for regulation by the several hundred microRNAs (miRNAs) encoded in the genome. The regulation occurs posttranscriptionally and involves the approximately 21-nucleotide miRNA interacting with a target site in the mRNA that generally has imperfect complementarity to the miRNA. The target sites are almost invariably in the 3'-untranslated region of the messenger RNA (mRNA), often in multiple copies. Metazoan miRNAs were previously thought to down-regulate protein expression by inhibiting target mRNA translation at some stage after the translation initiation step, without much effect on mRNA abundance. However, recent studies have questioned these suppositions. With some targets, an increase in the rate of mRNA degradation by the normal decay pathway contributes to the decrease in protein expression. miRNAs can also inhibit translation initiation, specifically the function of the cap-binding initiation factor, eIF4E. Repressed target mRNAs as well as miRNAs themselves accumulate in cytoplasmic foci known as P-bodies, where many enzymes involved in mRNA degradation are concentrated. However, P-bodies may also serve as repositories for the temporary and reversible storage of untranslated mRNA, and reducing the expression (knockdown) of several distinct P-body protein components can alleviate miRNA-mediated repression of gene expression.

Un microARN régule la production de neurones dopaminergiques dans le cerveau antérieur

“…Cette approche a montré qu'un seul des trois microARN candidats, miR-7a, est à la fois fortement exprimé dans la qui contrôlent l'activité post-transcriptionnelle des gènes et inhibent leur expression en bloquant la traduction des ARNm. Les microARN reconnaissent de courtes séquences spécifiques dans la partie 3'-UTR des ARNm en s'hybridant à une région complémentaire de six à huit nucléotides [8,9]. Pour cette raison nous avons cherché des microARN potentiellement capables de se fixer au 3'-UTR de Pax6 en utilisant des algorithmes de prédiction de cibles des microARN.…”

Incomplete penetrance and variable expressivity: is there a microRNA connection?

“…(49)(50)(51)(52)(53)(54)(55) In several instances, 3 0 UTR of a target gene may carry sites for multiple miRNAs, allowing for combinatorial regulation by these miRNAs. Recently, experimental evidence for the implied cooperativity of miRNAs acting on the same target has been reported.…”

“…(55) In the former case, miRNA and its target mRNA Number of genes retrieved from OMIM showing IP-VE. c Number of modifier genes taken from Surani et al (40) d Number of house-keeping genes used as control set (67) ( p value<0.05 IP-VE to control).…”

Smart functional nucleic acid chimeras: Enabling tissue specific RNA targeting therapy

“…91 The major regulation pathway in animals as well as in humans, is the translational repression induced by imperfect binding of the miRNA to complementary sites within the 3 0 untranslated regions of mRNA blocking the translation into a protein. 92,93 As imperfect target binding (compromised Watson-Crick base pairing rules) can block translation, one miRNA is able to regulate multiple www.tandfonline.com (85) mRNAs, making miRNAs an interesting tool for multi-target inhibition.…”