RNA Helicases as Shadow Modulators of Cell Cycle Progression.

Olga Sergeeva,Timofei Zatsepin

doi:10.3390/ijms22062984

Abstract

The progress of the cell cycle is directly regulated by modulation of cyclins and cyclin-dependent kinases. However, many proteins that control DNA replication, RNA transcription and the synthesis and degradation of proteins can manage the activity or levels of master cell cycle regulators. Among them, RNA helicases are key participants in RNA metabolism involved in the global or specific tuning of cell cycle regulators at the level of transcription and translation. Several RNA helicases have been recently evaluated as promising therapeutic targets, including eIF4A, DDX3 and DDX5. However, targeting RNA helicases can result in side effects due to the influence on the cell cycle. In this review, we discuss direct and indirect participation of RNA helicases in the regulation of the cell cycle in order to draw attention to downstream events that may occur after suppression or inhibition of RNA helicases.

Highlights

Cell division can be formally presented as a series of coordinated events that form the cell cycle
The interactions of certain cyclin-dependent kinases (CDK) and cyclins and a detailed description of the functions of each pair in cell cycle transitions have been summarized in recent reviews [2,3,4]
DDX3 directly interacts with pre-mRNA of transcription factor KLF4 and regulates its splicing. This event affects the gene expression of the key cell cycle regulators: cyclin A1 and cyclin-dependent kinase 2, which leads to the arrest of the cell cycle in the G1 phase [53]

Summary

Introduction

Cell division can be formally presented as a series of coordinated events that form the cell cycle. The interactions of certain CDKs and cyclins and a detailed description of the functions of each pair in cell cycle transitions have been summarized in recent reviews [2,3,4] Complex regulation of these key proteins occurs at all stages of their life cycle—transcription, translation, post-translational modification and proteolytic degradation mediated by ubiquitin. Inhibitors with more precise targeting to other cell cycle proteins have been tested in preclinical and clinical studies (MK-8776 and LY2606368 for check point kinase CHK1 and AZD1775 for WEE1) [11]. They still demonstrate a fairly low therapeutic index. We discuss the role of RNA helicases in the regulation of the cell cycle in order to draw attention to subsequent events that may occur after suppression or inhibition of RNA helicases

Basic Regulation of Cell Cycle

RNA Helicases in the Regulation of Cell Cycle

Conclusions