Decoding proteomic complexity of transcript variants and homologous isoforms for precision therapeutics.

Authors

Seo A Kum, Hong Koo Ha, Sun Sik Bae

Published in

The Korean journal of physiology & pharmacology : official journal of the Korean Physiological Society and the Korean Society of Pharmacology. Volume 30. Issue 6. Pages 521-542. Nov 01, 2026.

Abstract

The traditional "one gene, one protein" paradigm is insufficient to capture the vast phenotypic and physiological complexity of eukaryotes. This review aims to comprehensively elucidate the molecular mechanisms of transcriptomic diversification, namely, alternative splicing, alternative usage of promoter, and alternative polyadenylation, and their profound impacts on cellular homeostasis and human disease. By synthesizing recent breakthroughs in targeted long-read RNA sequencing, single-cell isoform-specific multiomics, and AI-driven 3D structural modeling, we systematically examine how transcript variants are generated and functionally annotated. Our analysis highlights that multiple transcript variants originating from a single genetic locus are not merely redundant copies; rather, subtle sequence alterations dynamically rewire protein-protein interaction networks and dictate precise subcellular localization. The exquisite spatiotemporal regulation of these variants controls critical cell fate decisions and organ development. Consequently, the pathological dysregulation of these processes, frequently termed spliceopathies, acts as a primary driver in severe pathologies, including cancer multidrug resistance, metabolic reprogramming, and neurodegenerative disorders. In conclusion, understanding the eukaryotic proteome requires a fundamental shift from conventional gene-level to isoform-level perspectives. Decoding the complex regulatory syntax of transcript variants paves the way for next-generation precision medicine, highlighting the therapeutic potential of RNA-targeted interventions, such as antisense oligonucleotides and CRISPR-based RNA editing, to correct pathogenic isoforms.

PMID:
42957433
Bibliographic data and abstract were imported from PubMed on 30 Oct 2026.

Read full publication at:
Please sign in to see all details.

Stats

1-terrible, 9-excellent. How would you rate this publication? Sign in in to submit your rating.

Post a comment

You need to be signed in to post comments. You can sign in here.

Comments

There are no comments yet.