Abstract
Gene expression is regulated at multiple levels in eukaryotic cells. Regulation at the post-transcriptional level is modulated by various trans-acting factors that bind to specific sequences in the messenger RNA (mRNA). The binding of different trans factors influences various aspects of the mRNA such as degradation rate, translation efficiency, splicing, localization, etc. MicroRNAs (miRNAs) are short endogenous ncRNAs that combine with the Argonaute to form the microRNA-induced silencing complex (miRISC), which uses base-pair complementation to silence the target transcript. RNA-binding proteins (RBPs) contribute to post-transcriptional control by influencing the mRNA stability and translation upon binding to cis-elements within the mRNA transcript. RBPs have been shown to impact gene expression through influencing the miRISC biogenesis, composition, or miRISC-mRNA target interaction. While there is clear evidence that those interactions between RBPs, miRNAs, miRISC and target mRNAs influence the efficiency of miRISC-mediated gene silencing, the exact mechanism for most of them remains unclear. This review summarizes our current knowledge on gene expression regulation through interactions of miRNAs and RBPs.
Highlights
The central dogma of biology follows the flow of genetic information; DNA is transcribed into RNA and RNA is translated into protein
A study that looked at the AU-rich elementbinding proteins (ARE-BPs), HuR, found that this RNA-binding proteins (RBPs) was able to mediate de-repression of Cat1 messenger RNA (mRNA) from microRNA-induced silencing complex (miRISC) silencing by binding to AU-rich elements (AREs) located next to miRNA binding sites (Kundu et al, 2012)
Dysregulation of miRISC-mediated gene silencing is prevalent in human diseases, especially in neurological disorders and cancers
Summary
The central dogma of biology follows the flow of genetic information; DNA is transcribed into RNA and RNA is translated into protein. It is proposed that FUS facilitates the association between miRISC components such as the Ago protein, a set of mature miRNAs, and interacting with their mRNA targets, increasing efficiency of miRNA-mediated silencing.
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