Abstract

microRNAs (miRNAs) are short ~22 nucleotides (nt) ribonucleic acids which post-transcriptionally regulate gene expression. miRNAs are key regulators of all cellular processes, and the correct expression of miRNAs in an organism is crucial for proper development and cellular function. As a result, the miRNA biogenesis pathway is highly regulated. In this review, we outline the basic steps of miRNA biogenesis and miRNA mediated gene regulation focusing on the role of RNA binding proteins (RBPs). We also describe multiple mechanisms that regulate the canonical miRNA pathway, which depends on a wide range of RBPs. Moreover, we hypothesise that the interaction between miRNA regulation and RBPs is potentially more widespread based on the analysis of available high-throughput datasets.

Highlights

  • MicroRNAs are an abundant class of small regulatory RNAs about 19–22 nucleotides in length [1]

  • We describe the characteristics and functions of RNA binding proteins (RBPs) that are necessary for the production of miRNAs and miRNA mediated gene expression as well as RBPs that regulate these processes in mammalian cells

  • A HITS-cross-linking and immonoprecipitation (CLIP) screening of RNA targets of DGCR8 in human cells revealed that DGCR8 binds to and mediates cleavage of small nucleolar RNAs [10]

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Summary

Introduction

MicroRNAs (miRNAs) are an abundant class of small regulatory RNAs about 19–22 nucleotides (nt) in length [1] They have been predicted to regulate the expression of more than 60% of mammalian genes and play fundamental roles in most biological processes including multiple diseases [2,3]. The maturation and function of miRNAs are highly dependent on the coordinated action of several RNA-binding proteins (RBP) [7] Some of these proteins present unique protein domains that are characteristic of proteins involved in small RNA processing and small RNA mediated gene regulatory events [8]. We have carried out a basic bioinformatics exercise to compute the potential scale of miRNA and RBP interactions using available CLIP data Based on this we suggest a more widespread interaction between RBPs and miRNA complexes in the targeting step of miRNA mediated gene regulation

Pri-miRNA Processing by the Microprocessor
Pre-miRNA Processing
RNA-Binding Proteins Involved in miRNA Mediated Gene Regulation
The Regulation of Pre-miRNA Processing
Regulation of the Turnover of Mature miRNAs
Materials and Methods
Findings
Conclusions
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