Alternative Transcripts Diversify Genome Function for Phenome Relevance to Health and Diseases

Area of Science:

• Molecular Biology
• Genetics
• Biochemistry

Background:

• Alternative RNA processing, including alternative exon splicing (AES), alternative transcription start (ATS), and alternative polyadenylation (APA) sites, is fundamental to generating transcript diversity in organisms.
• These mechanisms are pervasive, affecting at least 50% of human protein-coding genes and playing critical roles in cellular processes like proliferation and differentiation.

Purpose of the Study:

• To review the significance of AES, ATS, and APA in transcript diversity and its implications for health and disease.
• To highlight the impact of these RNA variants on protein identity, cellular functions, and developmental transitions.
• To discuss the interwoven nature of these processes and their dysregulation in various disorders and cancers.

Main Methods:

• Review of existing literature on alternative RNA processing mechanisms.
• Analysis of the impact of AES, ATS, and APA on gene expression and protein function.
• Discussion of challenges and potential solutions for genome-wide profiling of RNA variants.

Main Results:

• ATS and APA significantly impact protein identity by altering exon utilization, stability, and translation efficiency.
• AES, while having a limited effect on protein identity, is ubiquitous and can influence features like protein localization.
• These RNA variants exhibit high specificity for tissue type and developmental stage, underscoring their role in development and disease.

Conclusions:

• Dysregulation of AES, ATS, and APA contributes to a wide range of disorders and cancers.
• The interplay between these RNA processing mechanisms is complex, involving factors like RNA polymerase II and its CTD.
• Further research and improved genome-wide profiling methods are needed to fully understand and address the role of RNA variants in health and disease.