Reciprocal Links between Pre-messenger RNA 3'-End Processing and Genome Stability.

Area of Science:

• Molecular Biology
• Genetics
• Biochemistry

Background:

• Pre-messenger RNA (pre-mRNA) 3 -end processing, including cleavage and polyadenylation, is crucial for gene expression and is linked to transcription termination.
• DNA damage globally inhibits pre-mRNA 3 -end cleavage in both yeast and human cells, suggesting a coordinated cellular response.
• Emerging evidence reveals intricate connections between pre-mRNA 3 -end processing machinery and the maintenance of genome stability.

Purpose of the Study:

• To review the multifaceted relationship between pre-mRNA 3 -end processing and genome stability control.
• To elucidate how DNA damage impacts pre-mRNA processing pathways and vice versa.
• To highlight the evolutionary conservation and disease relevance of this interplay.

Main Methods:

• Literature review of recent findings on pre-mRNA 3 -end processing and DNA damage response.
• Analysis of gene regulation, including alternative polyadenylation (APA), under DNA damage conditions.
• Examination of the localization and function of pre-mRNA processing factors at DNA damage sites.

Main Results:

• DNA damage triggers global inhibition of pre-mRNA 3 -end cleavage.
• Specific DNA damage response (DDR) genes exhibit altered 3 -end processing or utilize APA upon DNA damage.
• Several pre-mRNA 3 -end processing factors play roles in preventing genome instability and are recruited to DNA damage sites.

Conclusions:

• The interplay between pre-mRNA 3 -end processing and genome stability is a conserved biological process.
• Dysregulation of this interplay can contribute to disease development.
• Understanding these connections offers insights into cellular responses to stress and potential therapeutic targets.