Human messenger RNA harbors widespread noncoding splice isoforms.

Area of Science:

• Molecular Biology
• Genomics
• Cancer Research

Background:

• Premessenger RNA from protein-coding genes commonly undergoes alternative splicing, producing diverse protein isoforms.
• The existence of noncoding splice isoforms within human mRNA derived from protein-coding genes was previously unexplored.

Purpose of the Study:

• To investigate the prevalence and characteristics of noncoding splice isoforms in human mRNA.
• To explore the role of these noncoding isoforms in tissue specificity, RNA processing, and cancer.

Main Methods:

• Bioinformatic analysis of human transcriptomic data.
• Identification and characterization of mRNA noncoding isoforms.
• Analysis of tissue distribution, association with RNA processing pathways, and cancer relevance.

Main Results:

• Discovery of 15,836 mRNA noncoding isoforms across 7,298 human protein-coding genes.
• These isoforms are primarily produced via alternative splicing and polyadenylation, exhibiting tissue-specific expression.
• Upregulation of mRNA noncoding isoforms in cancer, association with cancer hallmarks, and predictive value for patient survival.

Conclusions:

• Human mRNA harbors widespread noncoding splice isoforms, in addition to protein-coding ones.
• These noncoding isoforms play regulatory roles and are implicated in cancer progression.
• Highlights the functional duality of mRNA, accommodating both protein translation and regulatory noncoding functions.