Enterprise AI Analysis
Revisiting Noncoding RNAs: Emerging Coding Functions and Their Impact on Skeletal Muscle Development
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.
Executive Impact
Key metrics and findings that highlight the transformative potential of ncRNA research for advanced therapeutics and diagnostics.
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Genome Coding Capacity
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miRNA Length
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Ribosome-Related circRNAs Identified
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Muscle Proliferation Reduction Potential
Deep Analysis & Enterprise Applications
Select a topic to dive deeper, then explore the specific findings from the research, rebuilt as interactive, enterprise-focused modules.
ncRNAs Coding Mechanism Overview
Pri-miRNA/LncRNA/circRNA
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Ribo-seq / MALDI-TOF-MS
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Sucrose Gradient / Vector Construction
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Functions and Clinical Applications
| Name | Website | Species | Content |
|---|---|---|---|
| ORF finder | https://www.ncbi.nlm.nih.gov/orffinder/ | Universal | To evaluate the encoding capacity of RNA transcripts |
| PhyloCSF | https://github.com/mlin/PhyloCSF/wiki | Multispecies (any with genomic data) | PhyloCSF can be used for ORF and exon alignment |
| CNIT (Coding-Non-Coding Identifying Tool)⁸⁹ | http://cnit.noncode.org/CNIT/ | Vertebrates (human, mouse, rat) | To evaluate the encoding capacity of RNA transcripts |
| SORFs.org⁹⁰ | http://www.sorfs.org | Primarily vertebrates (human, mouse) | A new database of sORFs was identified using ribosome sequencing analysis |
| SmProt⁹¹ | https://smprot.biolead.ac.cn/ | Multispecies | Micropeptide databases collected from literature mining, known databases, ribosome binding analyses, and MS |
Translation Driving Mechanisms of ncRNAs
Pri-miRNA Formation
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LncRNA Splicing & Transcription
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EicRNA / EcRNA / CIRNA Translation
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m⁶A Modification (Mettl3/14, FTO/Alkbh5)
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Micropeptides are mostly less than 50 amino acids long, highlighting their distinct biological roles.
MLN
LncRNA-encoded MLN peptide regulates calcium transport in the sarcoplasmic reticulum, impacting muscle motility.
Case Study: SPAR Polypeptide for Muscle Regeneration
Summary: In 2017, scientists identified SPAR, a novel 90 amino acid polypeptide encoded by lncRNA LINC00961. SPAR localizes in late lysosomes and inhibits mTORC1 activity, promoting muscle regeneration in injured skeletal muscle.
Enterprise Learning: This highlights how specific lncRNA-encoded peptides can be therapeutic targets for enhancing tissue repair and could inform the development of novel regenerative therapies.
DWORF
LncRNA-encoded DWORF peptide acts as an activator of the SERCA pump, reducing myocardial contraction time.
circ-ZNF609
This circRNA regulates muscle cell proliferation and its downregulation significantly reduces muscle cell proliferation in Duchenne muscular dystrophy.
| ncRNAs | Species | Protein/peptide | Translation initiation driver | Identification, methods and tools | Main functions |
|---|---|---|---|---|---|
| LINC00948 | Human and mouse | MLN | sORF | Conserved analysis of ORF; in vitro transcription; FLAG tag fusion vector | MLN acts similar to PLNs and sarcolipins, acting directly on sarcoplasmic reticulum Ca²⁺-ATPase, preventing Ca²⁺ from entering the sarcoplasmic reticulum |
| LOC100507537 | Mouse | DWORF | sORF | PhyloCSF; polyclonal rabbit antibody was prepared; EGFP tag fusion vector | DWORF peptide can neutralize SERCA inhibitors and reduce muscle contraction time |
| LINC00961 | Human and mouse | SPAR | sORF | Tandem MS | SPAR can reduce mTORC1 activity and promote muscle regeneration |
| LncRNA MyolncR4 | Mouse and zebrafish | LEMP | sORF | Construction of HA tag vector | LEMP promotes muscle formation and regeneration in mouse |
| circ-ZNF609 | Human and mouse | / | IRES | Vector p-circ with a 3xFLAG tag; dual-luciferase reporting system; sucrose density gradient centrifugation | Controls myoblast proliferation |
| IncRNA-Six1 | Chicken | IncRNA-Six1-ORF2 | sORF | Vector PSDS-20218 with a 3×FLAG tag | Promots myoblast proliferation and migration |
| circEDC3 | Chicken | / | IRES and m⁶A motifs were predicted | ORF were found in circEDC3 | Inhibits myoblast proliferation, differentiation and apoptosis |
| circTmeff1 | Mouse | TMEFF1-339aa | IRES | TransCirc database (https://www.biosino.org/transcirc/); 3×FLAG tag fusion vector; dual-luciferase reporting system | Promote muscle atrophy |
| circNEB | Cattle | circNEB-peptide | / | Ribo-seq; P-EGFP-N1 fusion protein vector | circNEB-peptide promotes the proliferation and differentiation of bovine myoblasts through ubiquitination and myoblast fusion by directly interacting with SKP1 and TPM1 |
| CircKANSL1L | Pig | KANSL1L-551aa | / | KANSL1L-551aa with 3xFLAG tag | The circKANSL1L protein could activate the Akt-FoxO signaling pathway to regulate C2C12 differentiation |
Therapeutic Potential of ncRNA-Encoded Peptides
NcRNA-Encoded Peptides (MLN, DWORF, SPAR, TMEFF1-399aa, circDdb1-867aa, circNEB-peptide)
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Target Specific Muscle Functions (Contraction, Regeneration, Atrophy)
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Therapeutic Target Identification
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Drug Development & Clinical Applications
Promising
ncRNA-encoded peptides show promising potential as therapeutic agents for muscle atrophy and injury.
Case Study: circNEB-peptide for Muscle Repair
Summary: Overexpression of circNEB-peptide by injection of circNEB plasmid into cardiotoxin-injured mouse skeletal muscle promotes the repair of injured muscle.
Enterprise Learning: This demonstrates the potential of circRNAs as RNA therapies, delivering peptides to treat muscle injuries and offering a new avenue for drug development with potentially fewer side-effects.
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Your AI Implementation Roadmap
A phased approach to integrating AI-powered research and discovery into your enterprise, maximizing impact and minimizing disruption.
Phase 1: Discovery & Strategy Alignment
Conduct a deep dive into your current research workflows and identify high-impact areas for ncRNA-related AI application. Define clear objectives and success metrics for pilot programs.
Phase 2: Pilot Program & Platform Integration
Implement AI tools for predictive ncRNA analysis and peptide discovery in a controlled environment. Integrate findings with existing R&D platforms and validate initial results against experimental data.
Phase 3: Scaled Deployment & Iterative Refinement
Expand AI application across relevant departments, leveraging insights for drug development or biomarker identification. Continuously refine models based on new research and internal data, ensuring optimal performance.
Phase 4: Long-term Innovation & Competitive Advantage
Establish a dedicated AI research unit focused on emerging ncRNA coding functions. Drive continuous innovation, maintain a leading edge in therapeutic discovery, and secure long-term competitive advantage.
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