Posttranscriptional regulation of gene expression-adding another layer of complexity to the DNA damage response

Area of Science:

• Molecular Biology
• Cell Biology
• Genetics

Background:

• The DNA damage response (DDR) is a critical cellular network that orchestrates cell cycle arrest or apoptosis following DNA damage.
• The DDR traditionally involves rapid phosphorylation cascades and delayed transcriptional responses, including Cdk inhibitors like p21.
• Emerging evidence points to significant post-transcriptional regulatory mechanisms influencing the DDR.

Purpose of the Study:

• To review recent advancements in understanding the post-transcriptional regulation of the DDR.
• To emphasize the roles of non-coding RNAs and RNA-binding proteins (RBPs) in the DDR.
• To explore how DNA damage-activated protein kinases control RBP function within the DDR.

Main Methods:

• Literature review of recent research on DDR post-transcriptional regulation.
• Focus on studies involving non-coding RNAs, microRNAs (miRs), and RNA-binding proteins (RBPs).
• Analysis of kinase-mediated regulation of RBPs in response to genotoxic stress.

Main Results:

• The DDR is increasingly recognized to involve sophisticated post-transcriptional control layers.
• Non-coding RNAs and RBPs play significant roles in modulating the DDR, impacting cellular outcomes.
• DNA damage-activated kinases directly influence the activity and function of specific RBPs.

Conclusions:

• Post-transcriptional regulation by non-coding RNAs and RBPs represents a critical, yet incompletely understood, dimension of the DDR.
• Understanding RBP regulation by kinases is essential for a comprehensive view of the cellular response to DNA damage.
• Further research into these mechanisms holds promise for understanding cancer biology and developing therapeutic strategies.