scTEA-db: a comprehensive database of novel terminal exon isoforms identified from human single cell transcriptomes

Area of Science:

• Genomics
• Molecular Biology
• Bioinformatics

Background:

• Alternative terminal exons generate messenger RNA (mRNA) isoforms with distinct 3' untranslated regions (3' UTRs) and protein-coding sequences.
• These alternative 3' UTRs regulate crucial cellular processes like mRNA stability, translation, and localization, impacting cell identity and function.
• Previous research indicated that approximately 25% of observed RNA 3' ends are in intronic regions, suggesting many 3' end isoforms remain undiscovered.

Purpose of the Study:

• To identify and catalog previously unannotated terminal exons and their associated transcript isoforms.
• To create a comprehensive, accessible database (scTEA-db) for exploring these novel elements.
• To provide a foundation for investigating the functional roles of unannotated terminal exon isoforms in cellular processes and disease.

Main Methods:

• Analysis of 53,069 publicly available single-cell transcriptomes.
• Identification of novel terminal exons and transcript isoforms.
• Development of the single cell-based Terminal Exon Annotation database (scTEA-db) with a web portal for exploration.

Main Results:

• Discovery and annotation of 12,063 previously unannotated terminal exons.
• Identification of associated transcript isoforms for 5,538 human genes.
• The database includes novel terminal exons from 110 known human cancer driver genes.
• Inclusion of unannotated terminal exons showed higher tissue specificity compared to annotated ones.

Conclusions:

• The scTEA-db database significantly expands the known landscape of terminal exon isoforms.
• This resource facilitates research into the biological significance of novel isoforms in cell identity and function.
• The findings have implications for understanding gene regulation and potential therapeutic targets, particularly in cancer.