The Hidden Proteome of Cutaneous Repair: Emerging Roles of ncRNA-Encoded Micropeptides.

Authors

Sibei Tang, Li Li, Hanyu Dou, Xiaolei Ding, Dongqing Li, Dongsheng Jiang

Published in

American journal of physiology. Cell physiology. Sep 24, 2026. Epub Sep 24, 2026.

Abstract

The molecular mechanisms governing cutaneous repair have been largely understood through transcriptional and post-transcriptional regulatory networks. Recent discoveries, however, have challenged the long-held assumption that noncoding RNAs (ncRNAs) function exclusively as regulatory transcripts. Advances in translatomics have revealed that a subset of long noncoding RNAs (lncRNAs) and circular RNAs (circRNAs) encode bioactive micropeptides, uncovering a hidden proteome involved in tissue repair. In this mini-review, we discuss the established and potential roles of ncRNA-derived micropeptides in processes relevant to cutaneous repair, including re-epithelialization, fibroblast plasticity and matrix remodeling, inflammatory resolution and vascular repair. Rather than acting as isolated molecular effectors, these micropeptides operate across multiple biological scales, from intracellular protein signaling and cell-intrinsic programs to tissue remodeling and the broader repair microenvironment. We further highlight the emerging concept that a single ncRNA locus can generate distinct RNA- and peptide-mediated functions, thereby expanding the regulatory capacity of the noncoding genome. Finally, we discuss key unanswered questions, including what licenses context-specific micropeptide translation during tissue repair and how RNA and micropeptide outputs cooperate to shape repair outcomes. Together, these advances support an emerging conceptual framework in which the ncRNA-encoded hidden proteome constitutes an additional regulatory layer in cutaneous repair, providing new insights into unconventional mechanisms of tissue repair and potential opportunities for therapeutic intervention.

PMID:
42781502
Bibliographic data and abstract were imported from PubMed on 25 Sep 2026.

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