Role of 3’-untranslated region translational control in cancer development, diagnostics and treatment

Abstract

The messenger RNA 3’-untranslated region (3’UTR) plays an important role in regulation of gene expression on the posttranscriptional level. The 3’UTR controls gene expression via orchestrated interaction between the structural components of mRNAs (cis-element) and the specific trans-acting factors (RNA binding proteins and non-coding RNAs). The crosstalk of these factors is based on the binding sequences and/or direct protein-protein interaction, or just functional interaction. Much new evidence that has accumulated supports the idea that several RNA binding factors can bind to common mRNA targets: to the non-overlapping binding sites or to common sites in a competitive fashion. Various factors capable of binding to the same RNA can cooperate or be antagonistic in their actions. The outcome of the collective function of all factors bound to the same mRNA 3’UTR depends on many circumstances, such as their expression levels, affinity to the binding sites, and localization in the cell, which can be controlled by various physiological conditions. Moreover, the functional and/or physical interactions of the factors binding to 3’UTR can change the character of their actions. These interactions vary during the cell cycle and in response to changing physiological conditions. Abnormal functioning of the factors can lead to disease. In this review we will discuss how alterations of these factors or their interaction can affect cancer development and promote or enhance the malignant phenotype of cancer cells. Understanding these alterations and their impact on 3’UTR-directed posttranscriptional gene regulation will uncover promising new targets for therapeutic intervention and diagnostics. We will also discuss emerging new tools in cancer diagnostics and therapy based on 3’UTR binding factors and approaches to improve them.

Keywords: Translational control; 3’-untranslated region; MicroRNAs; RNA binding proteins; Cancer

Core tip: The messenger RNA 3’-untranslated region (3’UTR) plays an important role in regulation of gene expression on the posttranscriptional level. 3’UTR controls gene expression via orchestrated interaction between structural components mRNAs (cis-element) and specific trans-acting factors (RNA binding proteins and non-coding RNAs). Alteration of any of these components can lead to various pathologies. In this review we will discuss how alteration of these factors or a change in the crosstalk between them can affect cancer development and promote or enhance the malignant phenotype of cancer cells. Understanding these regulatory mechanisms and their impact on 3’UTR-directed posttranscriptional gene regulation may uncover promising new targets for therapeutic intervention and diagnostics.