From Translation to Causality: A Two-Axis Map of RNA-of-Origin and Output Attribution in Translated Non-Coding RNAs During Skeletal Muscle Myogenesis and Regeneration
Transcripts annotated as non-coding can yield both an RNA molecule and a translated product, complicating causal attribution in skeletal muscle. Three distinct claims require different evidence: a product exists, the nominated RNA generated it, and the product drives a defined phenotype. We examine them in myogenesis and regeneration using a qualitative, two-axis evidence map. The T axis records translation and RNA-of-origin evidence, whereas the F axis records experiments separating RNA-dependent from product-dependent effects for a stated model and endpoint. Endogenous coding-selective experiments support qualified product-dependent assignments for LINC00961–SPAR and MTLN/MPM. Linc-RAM/MRLN demonstrates biologically active RNA and peptide outputs, but not that both cause the same phenotype. Among the selected circRNA systems, circZNF609, circFAM188B, circNEB, and circSIK2 retain unresolved source and/or functional attribution, and none meets both T4 and F4. Rather than ranking study quality or assuming transfer across species and myogenic stages, the map identifies the experiment still needed to establish causality.
Authors
- Nanjian Luo (ORCID: https://orcid.org/0000-0002-4371-5378)
- Mingtao Ma (ORCID: https://orcid.org/0009-0000-1517-7384)
- Xixi Yang
- Yueying Zhang
- Keying Li
- Wei Zhang
Institutions
- Zunyi Medical University (CN)
Publication Details
- Journal
- Cells
- Published
- 2026-10-30
- DOI
- https://doi.org/10.3390/cells15211981
- Primary Topic
- Muscle Physiology and Disorders
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- Health Commission of Guizhou Province
- Guizhou Science and Technology Department