Characterization of RNA Editing in Oxidative and Glycolytic Skeletal Muscles of Yak
Simple Summary
Abstract
1. Introduction
2. Materials and Methods
2.1. Data Resource
2.2. Whole Genome Sequencing
2.3. Reads Mapping
2.4. RNA Editing Detection
2.5. Validation of RNA Editing Sites Through Sanger Sequencing
2.6. Analysis of the Impact of RNA Editing on miRNA Regulation
2.7. Pairwise Comparison of AG Sites Between Groups
2.8. Enrichment Analysis
2.9. Conservation Analysis of RNA Editing Sites
3. Results
3.1. Identification of RNA Editing Site in BF and OEA Muscles
3.2. Sequence Preference and Annotation of RNA Editing Sites in Muscle Tissue
3.3. Comparative Analysis of RNA Editing Between Yak and Human
3.4. Impact of RNA Editing on MiRNA Regulation
3.5. Analysis of Differential RNA Editing in BF and OEA Muscles
4. Discussion
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Data Availability Statement
Conflicts of Interest
Abbreviations
| BF | Biceps femoris |
| OEA | Obliquus externus abdominis |
| MyHC | Myosin heavy-chain |
| PPARgC1A(PGC-1α) | Proliferator Activated Receptor Gamma Coactivator 1 Alpha |
| MEF2C | Myocyte Enhancer Factor 2C |
| ADAR | Adenosine deaminases acting on RNA |
| A | Adenosine |
| I | Inosine |
| G | Guanine |
| C | Cytosine |
| T | Thymine |
| U | Uracil |
| UTR | Untranslated region |
| GO | Geneontology |
| KEGG | Kyoto Encyclopedia of Genes and Genomes |
| BLAST | Basic Local Alignment Search Tool |
| E | Expect |
| CDS | Coding DNA Sequence |
| BP | Biological process |
| CC | Cellular component |
| MF | Molecular function |
References
- Tian, J.-C.; Han, L.; Yu, Q.-L.; Shi, X.-X.; Wang, W.-T. Changes in Tenderness and Cathepsins Activity during Post Mortem Ageing of Yak Meat. Can. J. Anim. Sci. 2013, 93, 321–328. [Google Scholar] [CrossRef]
- Gao, M.-R.; Xu, Q.-D.; Zeng, W.-C. Effect of Tea Polyphenols on the Tenderness of Yak Meat. J. Food Process. Preserv. 2020, 44, e14433. [Google Scholar] [CrossRef]
- Listrat, A.; Lebret, B.; Louveau, I.; Astruc, T.; Bonnet, M.; Lefaucheur, L.; Picard, B.; Bugeon, J. How Muscle Structure and Composition Influence Meat and Flesh Quality. Sci. World J. 2016, 2016, 3182746. [Google Scholar] [CrossRef]
- Picard, B.; Gagaoua, M. Muscle Fiber Properties in Cattle and Their Relationships with Meat Qualities: An Overview. J. Agric. Food Chem. 2020, 68, 6021–6039. [Google Scholar] [CrossRef]
- Talbot, J.; Maves, L. Skeletal Muscle Fiber Type: Using Insights from Muscle Developmental Biology to Dissect Targets for Susceptibility and Resistance to Muscle Disease. Wiley Interdiscip. Rev. Dev. Biol. 2016, 5, 518–534. [Google Scholar] [CrossRef]
- Joo, S.T.; Kim, G.D.; Hwang, Y.H.; Ryu, Y.C. Control of Fresh Meat Quality Through Manipulation of Muscle Fiber Characteristics. Meat Sci. 2013, 95, 828–836. [Google Scholar] [CrossRef] [PubMed]
- Ryu, Y.C.; Choi, Y.M.; Lee, S.H.; Shin, H.G.; Choe, J.H.; Kim, J.M.; Hong, K.C.; Kim, B.C. Comparing the Histochemical Characteristics and Meat Quality Traits of Different Pig Breeds. Meat Sci. 2008, 80, 363–369. [Google Scholar] [CrossRef]
- Zhang, M.; Liu, Y.; Fu, C.; Wang, J.; Chen, S.; Yao, J.; Lai, S. Expression of MyHC Genes, Composition of Muscle Fiber Type and Their Association with Intramuscular Fat, Tenderness in Skeletal Muscle of Simmental Hybrids. Mol. Biol. Rep. 2014, 41, 833–840. [Google Scholar] [CrossRef]
- Wang, Y.; Zhang, D.; Liu, Y. Research Progress on the Regulating Factors of Muscle Fiber Heterogeneity in Livestock: A Review. Animals 2024, 14, 2225. [Google Scholar] [CrossRef]
- Farajollahi, S.; Maas, S. Molecular Diversity Through RNA Editing: A Balancing Act. Trends Genet. 2010, 26, 221–230. [Google Scholar] [CrossRef]
- Benne, R.; Van den Burg, J.; Brakenhoff, J.P.; Sloof, P.; Van Boom, J.H.; Tromp, M.C. Major Transcript of the Frameshifted coxII Gene from Trypanosome Mitochondria Contains Four Nucleotides That Are Not Encoded in the DNA. Cell 1986, 46, 819–826. [Google Scholar] [CrossRef]
- Nishikura, K. A-to-I Editing of Coding and Non-Coding RNAs by ADARs. Nat. Rev. Mol. Cell Biol. 2016, 17, 83–96. [Google Scholar] [CrossRef]
- Schmidt, J.W.; Wehde, B.L.; Sakamoto, K.; Triplett, A.A.; Anderson, S.M.; Tsichlis, P.N.; Leone, G.; Wagner, K.-U. Stat5 Regulates the Phosphatidylinositol 3-Kinase/Akt1 Pathway during Mammary Gland Development and Tumorigenesis. Mol. Cell. Biol. 2014, 34, 1363–1377. [Google Scholar] [CrossRef] [PubMed]
- Gott, J.M.; Emeson, R.B. Functions and mechanisms of RNA editing. Annu. Rev. Genet. 2000, 34, 499–531. [Google Scholar] [CrossRef]
- Wu, S.; Yang, M.; Kim, P.; Zhou, X. ADeditome Provides the Genomic Landscape of A-to-I RNA Editing in Alzheimer’s Disease. Brief. Bioinform. 2021, 22, bbaa384. [Google Scholar] [CrossRef] [PubMed]
- Eisenberg, E.; Levanon, E.Y. A-to-I RNA Editing—Immune Protector and Transcriptome Diversifier. Nat. Rev. Genet. 2018, 19, 473–490. [Google Scholar] [CrossRef] [PubMed]
- Gagnidze, K.; Rayon-Estrada, V.; Harroch, S.; Bulloch, K.; Papavasiliou, F.N. A New Chapter in Genetic Medicine: RNA Editing and Its Role in Disease Pathogenesis. Trends Mol. Med. 2018, 24, 294–303. [Google Scholar] [CrossRef]
- Ma, X.F.; Liu, A.J.; Zheng, Z.; Hu, B.X.; Zhi, Y.X.; Liu, C.; Tian, S.J. Resolving and Functional Analysis of RNA Editing Sites in Sheep Ovaries and Associations with Litter Size. Animal 2024, 18, 101342. [Google Scholar] [CrossRef]
- Cai, W.; Cole, J.B.; Goddard, M.E.; Li, J.; Zhang, S.; Song, J. Mammary Gland Multi-Omics Data Reveals New Genetic Insights into Milk Production Traits in Dairy Cattle. PLoS Genet. 2025, 21, e1011675. [Google Scholar] [CrossRef]
- Wu, X.; Zhou, X.; Chu, M.; Guo, X.; Pei, J.; Xiong, L.; Ma, X.; Bao, P.; Liang, C.; Yan, P. Whole Transcriptome Analyses and Comparison Reveal the Metabolic Differences between Oxidative and Glycolytic Skeletal Muscles of Yak. Meat Sci. 2022, 194, 108948. [Google Scholar] [CrossRef]
- Li, H.; Durbin, R. Fast and Accurate Short Read Alignment with Burrows–Wheeler Transform. Bioinformatics 2009, 25, 1754–1760. [Google Scholar] [CrossRef]
- Li, H.; Handsaker, B.; Wysoker, A.; Fennell, T.; Ruan, J.; Homer, N.; Marth, G.; Abecasis, G.; Durbin, R. 1000 Genome Project Data Processing Subgroup the Sequence Alignment/Map Format and SAMtools. Bioinformatics 2009, 25, 2078–2079. [Google Scholar] [CrossRef]
- Picard Tools—By Broad Institute. Available online: https://broadinstitute.github.io/picard/ (accessed on 6 October 2025).
- Kim, D.; Langmead, B.; Salzberg, S.L. HISAT: A Fast Spliced Aligner with Low Memory Requirements. Nat. Methods 2015, 12, 357–360. [Google Scholar] [CrossRef]
- Picardi, E.; Pesole, G. REDItools: High-Throughput RNA Editing Detection Made Easy. Bioinformatics 2013, 29, 1813–1814. [Google Scholar] [CrossRef] [PubMed]
- Picardi, E.; D’Erchia, A.M.; Montalvo, A.; Pesole, G. Using REDItools to Detect RNA Editing Events in NGS Datasets. Curr. Protoc. Bioinform. 2015, 49, 12.12.1–12.12.15. [Google Scholar] [CrossRef] [PubMed]
- Cingolani, P.; Platts, A.; Wang, L.L.; Coon, M.; Nguyen, T.; Wang, L.; Land, S.J.; Lu, X.; Ruden, D.M. A Program for Annotating and Predicting the Effects of Single Nucleotide Polymorphisms, SnpEff: SNPs in the Genome of Drosophila Melanogaster Strain W1118; Iso-2; Iso-3. Fly 2012, 6, 80–92. [Google Scholar] [CrossRef] [PubMed]
- McGeary, S.E.; Lin, K.S.; Shi, C.Y.; Pham, T.M.; Bisaria, N.; Kelley, G.M.; Bartel, D.P. The Biochemical Basis of microRNA Targeting Efficacy. Science 2019, 366, eaav1741. [Google Scholar] [CrossRef]
- John, B.; Enright, A.J.; Aravin, A.; Tuschl, T.; Sander, C.; Marks, D.S. Human MicroRNA Targets. PLoS Biol. 2004, 2, e363. [Google Scholar] [CrossRef]
- Raudvere, U.; Kolberg, L.; Kuzmin, I.; Arak, T.; Adler, P.; Peterson, H.; Vilo, J. g:Profiler: A Web Server for Functional Enrichment Analysis and Conversions of Gene Lists (2019 Update). Nucleic Acids Res. 2019, 47, W191–W198. [Google Scholar] [CrossRef]
- Xie, C.; Mao, X.; Huang, J.; Ding, Y.; Wu, J.; Dong, S.; Kong, L.; Gao, G.; Li, C.-Y.; Wei, L. KOBAS 2.0: A Web Server for Annotation and Identification of Enriched Pathways and Diseases. Nucleic Acids Res. 2011, 39, W316–W322. [Google Scholar] [CrossRef]
- Picardi, E.; D’Erchia, A.M.; Lo Giudice, C.; Pesole, G. REDIportal: A Comprehensive Database of A-to-I RNA Editing Events in Humans. Nucleic Acids Res. 2017, 45, D750–D757. [Google Scholar] [CrossRef]
- Tan, M.H.; Li, Q.; Shanmugam, R.; Piskol, R.; Kohler, J.; Young, A.N.; Liu, K.I.; Zhang, R.; Ramaswami, G.; Ariyoshi, K.; et al. Dynamic Landscape and Regulation of RNA Editing in Mammals. Nature 2017, 550, 249–254. [Google Scholar] [CrossRef]
- Bakhtiarizadeh, M.R.; Salehi, A.; Rivera, R.M. Genome-Wide Identification and Analysis of A-to-I RNA Editing Events in Bovine by Transcriptome Sequencing. PLoS ONE 2018, 13, e0193316. [Google Scholar] [CrossRef]
- Pinto, Y.; Cohen, H.Y.; Levanon, E.Y. Mammalian Conserved ADAR Targets Comprise Only a Small Fragment of the Human Editosome. Genome Biol. 2014, 15, R5. [Google Scholar] [CrossRef] [PubMed]
- Li, C.; Lv, W.; He, Z.; Pan, X.; Zeng, Y.; Mulder, J.; Sjöstedt, E.; Huang, Z.; Liu, W.; Xu, L.; et al. Landscape of A-I RNA Editing in Mouse, Pig, Macaque, and Human Brains. Nucleic Acids Res. 2025, 53, gkaf534. [Google Scholar] [CrossRef]
- Lu, X.; Ng, H.-H.; Bubulya, P.A. The role of SON in splicing, development and disease. Wiley Interdiscip. Rev. RNA 2014, 5, 637–646. [Google Scholar] [CrossRef]
- An, N.A.; Ding, W.; Yang, X.-Z.; Peng, J.; He, B.Z.; Shen, Q.S.; Lu, F.; He, A.; Zhang, Y.E.; Tan, B.C.-M.; et al. Evolutionarily Significant A-to-I RNA Editing Events Originated Through G-to-A Mutations in Primates. Genome Biol. 2019, 20, 24. [Google Scholar] [CrossRef]
- Zhang, Y.; Li, L.; Mendoza, J.J.; Wang, D.; Yan, Q.; Shi, L.; Gong, Z.; Zeng, Z.; Chen, P.; Xiong, W. Advances in A-to-I RNA Editing in Cancer. Mol. Cancer 2024, 23, 280. [Google Scholar] [CrossRef]
- Tang, S.J.; Shen, H.; An, O.; Hong, H.; Li, J.; Song, Y.; Han, J.; Tay, D.J.T.; Ng, V.H.E.; Bellido Molias, F.; et al. Cis- and Trans-Regulations of Pre-mRNA Splicing by RNA Editing Enzymes Influence Cancer Development. Nat. Commun. 2020, 11, 799. [Google Scholar] [CrossRef] [PubMed]
- Tajaddod, M.; Jantsch, M.F.; Licht, K. The Dynamic Epitranscriptome: A to I Editing Modulates Genetic Information. Chromosoma 2016, 125, 51–63. [Google Scholar] [CrossRef] [PubMed]
- Savva, Y.A.; Rieder, L.E.; Reenan, R.A. The ADAR Protein Family. Genome Biol. 2012, 13, 252. [Google Scholar] [CrossRef]
- Agarwal, M.; Sharma, A.; Kumar, P.; Kumar, A.; Bharadwaj, A.; Saini, M.; Kardon, G.; Mathew, S.J. Myosin Heavy Chain-Embryonic Regulates Skeletal Muscle Differentiation during Mammalian Development. Development 2020, 147, dev184507. [Google Scholar] [CrossRef] [PubMed]
- Bharadwaj, A.; Sharma, J.; Singh, J.; Kumari, M.; Dargar, T.; Kalita, B.; Mathew, S.J. Musculoskeletal Defects Associated with Myosin Heavy Chain-embryonic Loss of Function Are Mediated by the YAP Signaling Pathway. EMBO Mol. Med. 2023, 15, e17187. [Google Scholar] [CrossRef]
- Zeng, C.; Shi, H.; Kirkpatrick, L.T.; Ricome, A.; Park, S.; Scheffler, J.M.; Hannon, K.M.; Grant, A.L.; Gerrard, D.E. Driving an Oxidative Phenotype Protects Myh4 Null Mice from Myofiber Loss During Postnatal Growth. Front. Physiol. 2022, 12, 785151. [Google Scholar] [CrossRef]
- Rasbach, K.A.; Gupta, R.K.; Ruas, J.L.; Wu, J.; Naseri, E.; Estall, J.L.; Spiegelman, B.M. PGC-1α Regulates a HIF2α-Dependent Switch in Skeletal Muscle Fiber Types. Proc. Natl. Acad. Sci. USA 2010, 107, 21866–21871. [Google Scholar] [CrossRef] [PubMed]
- Vargas-Franco, D.; Kalra, R.; Draper, I.; Pacak, C.A.; Asakura, A.; Kang, P.B. The Notch Signaling Pathway in Skeletal Muscle Health and Disease. Muscle Nerve 2022, 66, 530–544. [Google Scholar] [CrossRef]
- Li, Y.; Wang, Y.; Yan, M.; Wu, S.; Liu, M.; Raza, S.H.A. Supplementary Feeding Regulates Muscle Development of Oula Sheep (Tibetan Sheep, Ovis aries) Through Glucose Metabolism Pathway. Animals 2025, 15, 2626. [Google Scholar] [CrossRef]
- Ueno, S.; Seino, Y.; Hidaka, S.; Nakatani, M.; Hitachi, K.; Murao, N.; Maeda, Y.; Fujisawa, H.; Shibata, M.; Takayanagi, T.; et al. Blockade of Glucagon Increases Muscle Mass and Alters Fiber Type Composition in Mice Deficient in Proglucagon-derived Peptides. J. Diabetes Investig. 2023, 14, 1045–1055. [Google Scholar] [CrossRef] [PubMed]
- Boyer, J.G.; Prasad, V.; Song, T.; Lee, D.; Fu, X.; Grimes, K.M.; Sargent, M.A.; Sadayappan, S.; Molkentin, J.D. ERK1/2 Signaling Induces Skeletal Muscle Slow Fiber-Type Switching and Reduces Muscular Dystrophy Disease Severity. JCI Insight 2019, 4, e127356. [Google Scholar] [CrossRef]
- Summermatter, S.; Thurnheer, R.; Santos, G.; Mosca, B.; Baum, O.; Treves, S.; Hoppeler, H.; Zorzato, F.; Handschin, C. Remodeling of Calcium Handling in Skeletal Muscle Through PGC-1α: Impact on Force, Fatigability, and Fiber Type. Am. J. Physiol.-Cell Physiol. 2012, 302, C88–C99. [Google Scholar] [CrossRef]
- Lin, J.; Wu, H.; Tarr, P.T.; Zhang, C.-Y.; Wu, Z.; Boss, O.; Michael, L.F.; Puigserver, P.; Isotani, E.; Olson, E.N.; et al. Transcriptional Co-Activator PGC-1α Drives the Formation of Slow-Twitch Muscle Fibres. Nature 2002, 418, 797–801. [Google Scholar] [CrossRef] [PubMed]
- Handschin, C.; Chin, S.; Li, P.; Liu, F.; Maratos-Flier, E.; LeBrasseur, N.K.; Yan, Z.; Spiegelman, B.M. Skeletal Muscle Fiber-Type Switching, Exercise Intolerance, and Myopathy in PGC-1α Muscle-Specific Knock-out Animals. J. Biol. Chem. 2007, 282, 30014–30021. [Google Scholar] [CrossRef]
- Potthoff, M.J.; Olson, E.N. MEF2: A Central Regulator of Diverse Developmental Programs. Development 2007, 134, 4131–4140. [Google Scholar] [CrossRef] [PubMed]
- Anderson, C.M.; Hu, J.; Barnes, R.M.; Heidt, A.B.; Cornelissen, I.; Black, B.L. Myocyte Enhancer Factor 2C Function in Skeletal Muscle Is Required for Normal Growth and Glucose Metabolism in Mice. Skelet. Muscle 2015, 5, 7. [Google Scholar] [CrossRef] [PubMed]
- Dos Santos, M.; Backer, S.; Auradé, F.; Wong, M.M.-K.; Wurmser, M.; Pierre, R.; Langa, F.; Do Cruzeiro, M.; Schmitt, A.; Concordet, J.-P.; et al. A Fast Myosin Super Enhancer Dictates Muscle Fiber Phenotype Through Competitive Interactions with Myosin Genes. Nat. Commun. 2022, 13, 1039. [Google Scholar] [CrossRef]





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Shi, Y.; Wu, X.; Liang, C.; Guo, X.; Ma, X.; Yan, P.; Chu, M.; Wu, X. Characterization of RNA Editing in Oxidative and Glycolytic Skeletal Muscles of Yak. Biology 2026, 15, 97. https://doi.org/10.3390/biology15010097
Shi Y, Wu X, Liang C, Guo X, Ma X, Yan P, Chu M, Wu X. Characterization of RNA Editing in Oxidative and Glycolytic Skeletal Muscles of Yak. Biology. 2026; 15(1):97. https://doi.org/10.3390/biology15010097
Chicago/Turabian StyleShi, Yilin, Xuemei Wu, Chunnian Liang, Xian Guo, Xiaoming Ma, Ping Yan, Min Chu, and Xiaoyun Wu. 2026. "Characterization of RNA Editing in Oxidative and Glycolytic Skeletal Muscles of Yak" Biology 15, no. 1: 97. https://doi.org/10.3390/biology15010097
APA StyleShi, Y., Wu, X., Liang, C., Guo, X., Ma, X., Yan, P., Chu, M., & Wu, X. (2026). Characterization of RNA Editing in Oxidative and Glycolytic Skeletal Muscles of Yak. Biology, 15(1), 97. https://doi.org/10.3390/biology15010097

