Transcriptome sequencing suggests that pre-mRNA splicing counteracts widespread intronic cleavage and polyadenylation

Area of Science:

• Molecular Biology
• Genetics
• Bioinformatics

Background:

• Alternative splicing (AS) and alternative polyadenylation (APA) are key post-transcriptional gene regulation mechanisms.
• Intronic polyadenylation (IPA) is observed in normal and disease states, often attributed to random pre-mRNA processing variations.

Purpose of the Study:

• To investigate the relationship between tissue-specific intronic polyadenylation sites and splicing patterns.
• To identify and characterize novel APA events within introns using large-scale RNA sequencing data.

Main Methods:

• Utilized the Genotype-Tissue Expression (GTEx) project's RNA sequencing data.
• Applied computational methods, including analysis of short reads with non-templated adenines, to identify APA events.
• Correlated intronic polyadenylation site expression with tissue-specific splicing.

Main Results:

• APA events are more prevalent in introns compared to exons.
• A significant fraction of IPA events were identified without associated AS, termed spliced polyadenylated introns (SPIs).
• IPA in composite and skipped terminal exons showed correlation with splicing, unlike SPIs.

Conclusions:

• SPIs may result from a dynamic interplay between APA and AS, where introns are spliced while being cleaved and polyadenylated.
• Cotranscriptional pre-mRNA splicing might act as a safeguard against premature transcription termination at intronic polyadenylation sites.