Abstract

Protein binding to the non-coding regions of mRNAs is relatively well characterized and its functionality has been described in many examples. New results obtained by high-throughput methods indicate that binding to the coding sequence (CDS) by RNA-binding proteins is also quite common, but the functions thereof are more obscure. As described in this review, CDS binding has a role in the regulation of mRNA stability, but it has also a more intriguing role in the regulation of translational efficiency. Global approaches, which suggest the significance of CDS binding along with specific examples of CDS-binding RBPs and their modes of action, are outlined here, pointing to the existence of a relatively less-known regulatory network controlling mRNA stability and translation on yet another level.

Highlights

  • RNA-binding proteins (RBPs) regulate mRNA expression on many levels

  • 50 UTR has been linked to the regulation of translation initiation and there are numerous examples of it [2], 30 UTR is widely considered as the hub of mRNA stability regulation [3]

  • The regulation of mRNA stability is a well-known function of RBPs, it was usually attributed to 30 UTR binding sites [14]

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Summary

Introduction

RNA-binding proteins (RBPs) regulate mRNA expression on many levels. They are associated with 50 UTR or 30 UTR-binding; these non-coding regions have a longestablished regulatory role and have been demonstrated to regulate pre-mRNA splicing, cleavage and polyadenylation, RNA stability, RNA localization, RNA editing, and translation. There is mounting evidence that protein-coding regions are targeted by some RBPs. What is the role of this binding?. The mRNA coding sequence was, considered non-regulatory and was supposed not to interact with proteins. New data challenge this view, and, —For the moment—There are not many examples of the resolved regulatory mechanisms of the CDS-binding, the list is growing.

Global Approaches to Characterizing RBP-Binding Sites Suggest a Significant
Evolutionary Constraints to CDS Binding
Structural Elements in Coding Sequence Are Conserved and Bind RBPs
Functionality of CDS Binding
Proposed functions
CRD-BP
Ribosome Stalling and Its Role in Regulating Translation
Findings
Conclusions
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