Micropeptides Encoded by Noncoding RNAs: Biological Functions and Roles in Diseases

Traditionally considered noncoding, various classes of noncoding RNAs (ncRNAs)-including long noncoding RNAs (lncRNAs), circular RNAs (circRNAs), primary microRNAs (pri-miRNAs), ribosomal RNAs (rRNAs), and mRNA untranslated regions (UTRs)-have recently been shown to harbor micropeptide-encoding capacity. These functionally versatile micropeptides participate in various cellular processes spanning RNA modification, transcription regulation, splicing machinery, protein translation, and posttranslational modifications. This review systematically examines 3 aspects of ncRNA-derived micropeptides: their genomic origins and biogenesis, mechanistic roles in cellular physiology, and implications in human pathologies including oncogenesis, cardiovascular disorders, and neurodegenerative conditions. We highlight emerging potential as novel therapeutic targets and diagnostic biomarkers. Furthermore, we also discuss current methodologies for micropeptide and functional characterization. In summary, the systematic identification and annotation of disease-related ncRNA-encoded micropeptides has opened up a new milestone in the field for the development of novel targeted therapies and personalized disease treatment strategies.