DNA damage: RNA-binding proteins protect from near and far

Area of Science:

• Molecular Biology
• Genetics
• Biochemistry

Background:

• Recent large-scale genetic and molecular analyses highlight RNA-binding proteins (RBPs) as crucial in maintaining genome stability.
• RBPs play a significant role in preventing the formation of harmful RNA/DNA hybrids.
• These proteins are integral to the DNA damage response (DDR), influencing DNA repair and cell survival pathways.

Purpose of the Study:

• To elucidate the multifaceted roles of RBPs in genome stability and DNA damage response.
• To understand how RBPs regulate DNA damage response genes at the post-transcriptional level.
• To explore the interplay between RBP activity, RNA metabolism, and DNA repair mechanisms.

Main Methods:

• Large-scale genetic and molecular analyses.
• Investigation of RBP binding to mRNAs, nascent transcripts, noncoding RNAs, and damaged DNA.
• Analysis of RBP localization and binding dynamics following DNA damage.

Main Results:

• RBPs are identified as key regulators preventing genome instability and harmful RNA/DNA hybrids.
• Specific RBPs selectively control DNA damage response (DDR) genes via post-transcriptional mechanisms (splicing, polyadenylation, mRNA stability, translation).
• RBPs are directly implicated in DNA repair processes and their localization/binding is altered by DNA damage.

Conclusions:

• RBPs are central to preventing genome instability through diverse mechanisms, including managing RNA/DNA hybrids and participating in DDR.
• RBPs exhibit complex regulatory functions, impacting RNA metabolism and DNA repair at multiple levels.
• The dynamic nature of RBP binding and localization upon DNA damage suggests a coordinated regulation of both RNA and DNA metabolism to ensure cell survival.