Shi, Q.; Li, H.; Song, J.; Wu, H.; Zeng, Y.; Jiang, J.; Li, S.; Chen, Z.; He, X.

Pre-messenger RNA transcribed from canonical protein-coding genes is frequently alternatively spliced into diverse mature mRNA isoforms, thus translating into various protein products. However, it remains unknown whether human mRNA from a protein-coding gene harbors noncoding splice isoforms in the genome. Herein, we discovered 15,836 mRNA noncoding splice isoforms across 7,298 protein-coding genes in human. mRNA noncoding isoforms are mainly produced by alternative splicing and polyadenylation, which display tissue-specific distributions and involve in RNA processing pathways. Notably, mRNA noncoding isoforms are frequently upregulated in cancer. Differentially expressed mRNA noncoding isoforms are associated with the cancer hallmarks and can independently predict patient survival. These findings unraveled human mRNA harbors widespread noncoding splice isoforms, and highlight the dual characters of mRNA including protein-translation isoforms and noncoding splice isoforms, providing a new dimension to our understanding of mRNA functional property.