# Revisiting noncoding RNAs: emerging coding functions and their impact on skeletal muscle development

## TL;DR

Noncoding RNAs can produce peptides that influence muscle development and may offer new treatments for muscle diseases.

## Contribution

This work systematically evaluates tools for predicting ncRNA-encoded peptides and highlights their roles in skeletal muscle biology.

## Key findings

- ncRNA-encoded peptides regulate calcium transport in muscle cells, affecting contraction and growth.
- Ribosome profiling and mass spectrometry confirmed the translation of peptides from ncRNAs in skeletal muscle.
- ncRNA-derived peptides represent potential therapeutic targets for muscle-related disorders.

## Abstract

Accumulating evidence has revealed noncoding RNAs (ncRNAs) as versatile regulators in skeletal muscle development, extending beyond their canonical roles as nontranslating transcripts. Recent advancements in proteomics and translatomics have demonstrated that ncRNAs containing cryptic open reading frames can encode peptides/proteins. Here we systematically evaluate computational tools and databases for predicting ncRNA-encoded products, dissect the molecular mechanisms underlying their translation and synthesize the current landscape of ncRNA-derived peptides/proteins identified in skeletal muscle across species. We further discuss their emerging roles in myogenesis and potential clinical implications for muscle-related disorders. By highlighting the dual functionality of ncRNAs as both regulatory RNAs and peptide/protein precursors, this work provides a comprehensive resource for understanding the expanding complexity of skeletal muscle development and proposes novel therapeutic targets for muscle diseases.

The study explores the role of noncoding RNAs (ncRNAs) in muscle development and disease. Here, we address the gap in understanding how these ncRNA-encoded peptides function in muscle biology. Researchers reviewed methods to predict and validate the protein-coding potential of ncRNAs. They used bioinformatics tools to identify small open reading frames within ncRNAs, which are sequences that can potentially code for proteins. Techniques such as ribosome profiling (Ribo-seq) and mass spectrometry were employed to confirm the presence of these peptides. The findings reveal that ncRNA-encoded peptides play crucial roles in muscle development and may offer new therapeutic targets for muscle diseases. For instance, some peptides regulate calcium transport in muscle cells, affecting contraction and growth. The study concludes that understanding ncRNA-encoded peptides could lead to novel treatments for muscle disorders.

This summary was initially drafted using artificial intelligence, then revised and fact-checked by the author.