DEAD-Box RNA Helicases in Cell Cycle Control and Clinical Therapy

Abstract

Cell cycle is regulated through numerous signaling pathways that determine whether cells will proliferate, remain quiescent, arrest, or undergo apoptosis. Abnormal cell cycle regulation has been linked to many diseases. Thus, there is an urgent need to understand the diverse molecular mechanisms of how the cell cycle is controlled. RNA helicases constitute a large family of proteins with functions in all aspects of RNA metabolism, including unwinding or annealing of RNA molecules to regulate pre-mRNA, rRNA and miRNA processing, clamping protein complexes on RNA, or remodeling ribonucleoprotein complexes, to regulate gene expression. RNA helicases also regulate the activity of specific proteins through direct interaction. Abnormal expression of RNA helicases has been associated with different diseases, including cancer, neurological disorders, aging, and autosomal dominant polycystic kidney disease (ADPKD) via regulation of a diverse range of cellular processes such as cell proliferation, cell cycle arrest, and apoptosis. Recent studies showed that RNA helicases participate in the regulation of the cell cycle progression at each cell cycle phase, including G1-S transition, S phase, G2-M transition, mitosis, and cytokinesis. In this review, we discuss the essential roles and mechanisms of RNA helicases in the regulation of the cell cycle at different phases. For that, RNA helicases provide a rich source of targets for the development of therapeutic or prophylactic drugs. We also discuss the different targeting strategies against RNA helicases, the different types of compounds explored, the proposed inhibitory mechanisms of the compounds on specific RNA helicases, and the therapeutic potential of these compounds in the treatment of various disorders.

Aberrant cortical development is driven by impaired cell cycle and translational control in a DDX3X syndrome model

“…DDX3X mutations have also been linked to cancer progression, including medulloblastoma ( Jones, 2012 ; Pugh, 2012 ; Robinson et al, 2012 ), many of which overlap with ID-associated mutations. This oncogenic role is consistent with conserved functions of DDX3X in cell cycle progression ( Chen et al, 2016a ; Kotov et al, 2016 ; Li et al, 2014 ; Zhang and Li, 2021 ). Notably, cell cycle duration is also strongly implicated in cortical development ( Arai et al, 2011 ; Lange et al, 2009 ; Pilaz et al, 2016 ; Pilaz et al, 2009 ).…”

Aberrant cortical development is driven by impaired cell cycle and translational control in aDDX3Xsyndrome model

“…DDX3X mutations have also been linked to cancer progression, including medulloblastoma (Jones et al 2012; Pugh et al 2012; Robinson et al 2012), many of which overlap with ID-associated mutations. This oncogenic role is consistent with conserved functions of DDX3X in cell cycle progression (Li et al 2014; Chen et al 2016a; Kotov et al 2016; Zhang and Li 2021). Notably, cell cycle duration is also strongly implicated in cortical development (Lange et al 2009; Pilaz et al 2009; Arai et al 2011; Pilaz et al 2016).…”

DDX17 modulates the expression and alternative splicing of genes involved in apoptosis and proliferation in lung adenocarcinoma cells

“…The DEAD-box RNA helicases are the largest family of RNA helicases that play a signi cant role in all aspects of RNA metabolism, including the regulation of gene expression and AS [42][43][44] . DDX17, a DEADbox ATPase, is highly expressed in many types of human cancers, where it participates in tumor initiation, progression, and metastasis 11,13−15 .…”