DEAD-Box RNA Helicases and Genome Stability

Abstract

DEAD-box RNA helicases are important regulators of RNA metabolism and have been implicated in the development of cancer. Interestingly, these helicases constitute a major recurring family of RNA-binding proteins important for protecting the genome. Current studies have provided insight into the connection between genomic stability and several DEAD-box RNA helicase family proteins including DDX1, DDX3X, DDX5, DDX19, DDX21, DDX39B, and DDX41. For each helicase, we have reviewed evidence supporting their role in protecting the genome and their suggested mechanisms. Such helicases regulate the expression of factors promoting genomic stability, prevent DNA damage, and can participate directly in the response and repair of DNA damage. Finally, we summarized the pathological and therapeutic relationship between DEAD-box RNA helicases and cancer with respect to their novel role in genome stability.

Contribution of DEAD-Box RNA Helicase 21 to the Nucleolar Localization of Porcine Circovirus Type 4 Capsid Protein

“…DEAD-box RNA helicases are a myriad of multifunctional enzymes that control multiple processes of RNA metabolism, such as transcription, processing, and modification (Linder and Jankowsky, 2011;Zhang et al, 2011;Hao et al, 2019;Cargill et al, 2021;Ullah et al, 2021). Sometimes, these proteins function in microRNA processing, RNA nuclear transport and decoy as well (Diot et al, 2016).…”

DEAD-Box RNA Helicases DDX3X and DDX5 as Oncogenes or Oncosuppressors: A Network Perspective

“…DDX3X is mainly localized in the cytoplasm, but consistent with its numerous associated functions, it has been described to actively shuttle between the nucleus and the cytoplasm [ 15 ]. Besides the general roles in the RNA metabolism shared with other DEAD-box proteins, DDX3X has gained particular attention due to its role in viral infections [ 16 ] and in the maintenance of genomic stability by playing an active role in the response and repair of DNA damages [ 10 , 17 ]. Moreover, a large body of data published over the years has demonstrated the roles of DDX3X in cancer biology [ 18 ].…”

“…Mutations in helicase genes have been linked to vital functions as they lead to different chromosomal instabilities associated with neurological and neurodevelopment disorders or to hereditary diseases. Furthermore, recent reports have highlighted that RNA helicases play a central role in the maintenance of genome stability by regulating the expression of genes that are important for DNA damage repair or by direct involvement in the processing of complex nucleic acid species such as DNA–RNA hybrids, R-loops and telomeric sequences [ 10 ]. Therefore, it is not surprising that DEAD-box helicases have been implicated in cellular proliferation and/or neoplastic transformation of various types of tumors and are considered a new attractive target for the development of novel pharmaceutical anticancer drugs [ 11 ].…”

Role of Nuclear Non-Canonical Nucleic Acid Structures in Organismal Development and Adaptation to Stress Conditions

“…This result was expected because the nucleolus is one of the hotspots for R-loop formation ( Sollier et al, 2014 ). Some proteins of the DEAD-box family, which are known to be involved in R-loop regulation and bind RNAs were also enriched ( Cargill et al, 2021 ). Interestingly, the knockdown of several members of the DEAD-box family leads to the overexpression of genes involved in cell fate commitment and neuronal differentiation ( Wu et al, 2021 ), suggesting that the R-loops regulated by these proteins may be important for the pluripotency of mESC.…”