Ho Chul Woong, Lee Ji Won, Shin Chang Hoon, Min Kyung-Won
Department of Biology, College of Natural Sciences, Gangneung-Wonju National University, Gangneung-si 25457, Republic of Korea.
Department of Oncology Science, University of Oklahoma, Oklahoma City, OK 73104, USA.
Int J Mol Sci. 2025 Jun 19;26(12):5913. doi: 10.3390/ijms26125913.
The discovery of functional micropeptides encoded by long noncoding RNAs (lncRNAs) has challenged the traditional view that these transcripts lack coding potential. With the advancement of high-resolution translation profiling combined with enhanced MS-based techniques, numerous lncRNAs have been found to harbor small open reading frames (sORFs) that give rise to bioactive micropeptides. These peptides participate in diverse biological processes, particularly in cellular metabolism, by modulating enzymatic activity and metabolic pathways. However, the identification and functional characterization of these micropeptides remain technically challenging due to their small size, low abundance, and the need for rigorous downstream validation studies. This review encompasses a comprehensive overview of the biogenesis of lncRNA-derived micropeptides, methodologies for detecting and validating their expression, the molecular mechanisms governing their translation, and their emerging roles in metabolic regulation. By integrating current findings and technological advancements, we highlight the potential physiological and pathological implications of these micropeptides and outline future research directions in the field.
由长链非编码RNA（lncRNA）编码的功能性微肽的发现，挑战了传统观点，即这些转录本缺乏编码潜力。随着高分辨率翻译谱分析与基于质谱的增强技术的发展，已发现众多lncRNA含有小开放阅读框（sORF），这些小开放阅读框可产生具有生物活性的微肽。这些肽通过调节酶活性和代谢途径参与多种生物学过程，特别是细胞代谢。然而，由于这些微肽尺寸小、丰度低且需要严格的下游验证研究，其鉴定和功能表征在技术上仍然具有挑战性。本综述全面概述了lncRNA衍生微肽的生物发生、检测和验证其表达的方法、控制其翻译的分子机制及其在代谢调节中的新作用。通过整合当前的研究结果和技术进步，我们强调了这些微肽潜在的生理和病理意义，并概述了该领域未来的研究方向。
