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Regulation and different functions of the animal microRNA-induced silencing complex

期刊

出版社

WILEY
DOI: 10.1002/wrna.1701

关键词

Argonaute; gene regulation; microRNA; miRISC; small RNA

资金

  1. Natural Sciences and Engineering Research Council
  2. Canadian Institutes of Health Research

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miRNAs play a key role in gene expression regulation by forming the miRNA induced silencing complex (miRISC) with Argonaute protein to target specific mRNAs. The regulation of miRISC functions in animals involves post-translational modifications, 3' UTR environment, and interactions with other proteins. Subcellular localization and vesicular trafficking also play important roles in modulating miRISC function.
Among the different types of small RNAs, microRNAs (miRNAs) are key players in controlling gene expression at the mRNA level. To be active, they must associate with an Argonaute protein to form the miRNA induced silencing complex (miRISC) and binds to specific mRNA through complementarity sequences. The miRISC binding to an mRNA can lead to multiple outcomes, the most frequent being inhibition of the translation and/or deadenylation followed by decapping and mRNA decay. In the last years, several studies described different mechanisms modulating miRISC functions in animals. For instance, the regulation of the Argonaute protein through post-translational modifications can change the miRISC gene regulatory activity as well as modulate its binding to proteins, mRNA targets and miRISC stability. Furthermore, the presence of RNA binding proteins and multiple miRISCs at the targeted mRNA 3 ' untranslated region (3 ' UTR) can also affect its function through cooperation or competition mechanisms, underlying the importance of the 3 ' UTR environment in miRNA-mediated repression. Another way to regulate the miRISC function is by modulation of its interactors, forming different types of miRNA silencing complexes that affect gene regulation differently. It is also reported that the subcellular localization of several components of the miRNA pathway can modulate miRISC function, suggesting an important role for vesicular trafficking in the regulation of this essential silencing complex. This article is categorized under: RNA Interactions with Proteins and Other Molecules > RNA-Protein Complexes Regulatory RNAs/RNAi/Riboswitches > RNAi: Mechanisms of Action Regulatory RNAs/RNAi/Riboswitches > Biogenesis of Effector Small RNAs

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