From non-coding to coding: The importance of long non-coding RNA translation in de novo gene birth

• Published in: Biochimica et biophysica acta. General subjects Vol. 1869; no. 2; p. 130747
• Main Authors: Shiraishi, Taichi, Matsumoto, Akinobu
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.02.2025
• Subjects: Animals; De novo gene birth; Evolution, Molecular; Humans; Long non-coding RNA; Open Reading Frames; Polypeptide; Protein Biosynthesis; Ribo-seq; RNA, Long Noncoding - genetics; Translation; Translation initiation site detection by translation complex analysis; Translation; De novo gene birth; Translation initiation site detection by translation complex analysis; Polypeptide; Ribo-seq; Long non-coding RNA
• ISSN: 0304-4165; 1872-8006; 1872-8006
• DOI: 10.1016/j.bbagen.2024.130747

Recent emerging evidence demonstrates that some long non-coding RNAs (lncRNAs) can indeed be translated into functional polypeptides. These discoveries are pivotal for understanding de novo gene birth, the process by which new genes evolve from previously non-genic regions. In this review, we first introduce key methods, such as Ribo-seq and translation initiation site detection by translation complex analysis, for identifying coding sequences within lncRNAs and highlight examples of functional polypeptides derived from lncRNAs across species. These polypeptides play essential roles in maintaining cellular homeostasis and contribute to pathological processes, including cancer. However, because not all lncRNA-derived polypeptides appear to be functional, these lncRNAs may act as gene reservoirs. We also discuss how lncRNAs change their intracellular localization, how lncRNA-derived polypeptides evade immune surveillance, and how they gradually evolve into typical coding RNAs, providing evidence for the evolutionary model of de novo gene birth. [Display omitted] •Ribo-seq and TISCA are powerful NGS methods for uncovering hidden CDSs in lncRNAs.•Polypeptides from lncRNAs are crucial for maintaining homeostasis in organisms from yeast to mammals.•The “de novo gene birth” model suggests non-functional lncRNAs may evolve into coding RNAs.•Nascent genes from lncRNAs show strong evolutionary signatures and are believed to impact organism evolution.