Abstract：Skeletal muscle is an important tissue of human and livestock. The study of the muscle development is of great significance for treating muscle diseases and improving livestock meat quality. The process of muscle development is controlled by several myogenic transcription factors and signaling pathways. In addition, recent findings established that several noncoding RNAs play a critical role in the regulation of muscle development such as long non-coding RNA (lncRNA), microRNA (miRNA) and circular RNA (circRNA), etc. The detailed mechanism of muscle development is not well understood. Transfer RNAs (tRNAs) are fundamental components in the translation machinery as an adaptor molecule, and tRNA pool could be differentially exploited to modulate expression of mRNAs. In addition, tRNA can be cleaved into tRNA-derived fragments (tRFs) by a variety of ribonucleases (RNases) upon various stress conditions. Unlike the post-transcriptional regulation of lncRNA and miRNA on muscle development, tRNA has been implicated in various aspects of muscle development. Mitochondria play a central role in a plethora of processes related to the maintenance of muscle cellular homeostasis and genomic integrity. Mitochondrial tRNA(mt-tRNA) gene mutations lead to multiple myopathy because human mitochondrial genome is extremely small. The regulation of tRF is similar to miRNAs in regards to the related physiological processes, but are more conservative than miRNA. It is generally believed that tRF has strong tissue specificity, disease specificity and temporal specificity. Some skeletal muscle-specific tRFs could act post-transcriptionally via RNAi or targeting related genes. However, the tRF-sequencing analysis and functional mechanism of tRF are rarely studied in skeletal muscles. The myopathy caused by mitochondrial tRNA gene mutations are particularly complex, which are one of the challenges to diagnose, treat, or prevent diseases. Compared with other noncoding RNAs, the structural complexity of tRF also brings great challenges to data mining and analysis. In this review, we summarize the formation and function of tRNA and tRF especially in muscle development, which will deepen our understandings of related myopathy, and provide new ideas and directions for the investigation of skeletal muscle.
伊旭东, 赵甜甜, 庞卫军. tRNA及其衍生物对骨骼肌发育的作用[J]. 中国生物化学与分子生物学报, 2021, 37(9): 1180-1187.
YI Xu-Dong, ZHAO Tian-Tian, PANG Wei-Jun. Effects of tRNA and tRNA-derived Fragments on Skeletal Muscle Development. Chinese Journal of Biochemistry and Molecular Biol, 2021, 37(9): 1180-1187.
 Chen R, Lei S, Jiang T, et al. Roles of lncRNAs and circRNAs in regulating skeletal muscle development[J]. Acta Physiol(Oxf), 2020, 228(2): e13356  Jiang L, Liu Z, Wang Z, et al. Development of methods for detecting the fate of mesenchymal stem cells regulated by bone bioactive materials[J]. Bioact Mater, 2020, 6(3): 613-626  魏彩虹, 吴明明, 刘瑞凿, 等. 肌肉发育相关LncRNA的研究进展[J].中国农业科学(Wei CH, Wu MM, Liu RZ, et al. Research Progress in Muscular Growth and Development of Long Noncoding RNAs[J]. Sci Agric Sin), 2014, 47(20): 4078-4085  Wang J, Yang LZ, Zhang JS, et al. Effects of microRNAs on skeletal muscle development[J]. Gene, 2018, 668: 107-113  Das A, Das A, Das D, et al. Circular RNAs in myogenesis[J]. Biochim Biophys Acta Gene Regul Mech, 2020, 1863(4): 194372  Oberbauer V, Schaefer MR. tRNA-Derived Small RNAs: Biogenesis, Modification, Function and Potential Impact on Human Disease Development[J]. Genes(Basel), 2018, 9(12): 607  Światowy W, Jagodzińśki PP. Molecules derived from tRNA and snoRNA: Entering the degradome pool[J]. Biomed Pharmacother, 2018, 108: 36-42  Schimmel P. The emerging complexity of the tRNA world: mammalian tRNAs beyond protein synthesis[J]. Nat Rev Mol Cell Bio, 2018, 19(1): 45-58  Liapi E, van Bilsen M, Verjans R, et al. tRNAs and tRNA fragments as modulators of cardiac and skeletal muscle function[J]. Biochim Biophys Acta Mol Cell Res, 2020, 1867(3): 118465  Kimura S, Srisuknimit V, Waldor MK. Probing the diversity and regulation of tRNA modifications[J]. Curr Opin Microbiol, 2020, 57: 41-48  Rajendran V, Kalita P, Shukla H, et al. Aminoacyl-tRNA synthetases: Structure, function, and drug discovery[J]. Int J Biol Macromal, 2018, 111: 400-414  Kirchner S, Ignatova Z. Emerging roles of tRNA in adaptive translation, signalling dynamics and disease[J]. Nat Rev Genet, 2015, 16(2): 98-112  Kumar P, Kuscu C, Dutta A. Biogenesis and Function of Transfer RNA-Related Fragments (tRFs)[J]. Trends Biochem Sci, 2016, 41(8): 679-689  Cole C, Sobala A, Lu C, et al. Filtering of deep sequencing data reveals the existence of abundant Dicer-dependent small RNAs derived from tRNAs[J]. RNA, 2009, 15(12): 2147-2160  Lee YS, Shibata Y, Malhotra A, et al. A novel class of small RNAs: tRNA-derived RNA fragments (tRFs)[J]. Genes Dev, 2009, 23(22): 2639-2649  Haussecker D, Huang Y, Lau A, et al. Human tRNA-derived small RNAs in the global regulation of RNA silencing[J]. RNA, 2010, 16(4): 673-695  Kumar P, Mudunuri SB, Anaya J, et al. tRFdb: a database for transfer RNA fragments[J]. Nucleic Acids Res, 2015, 43(Database issue): D141-D145  Pliatsika V, Loher P, Magee R, et al. MINTbase v2.0: a comprehensive database for tRNA-derived fragments that includes nuclear and mitochondrial fragments from all The Cancer Genome Atlas projects[J]. Nucleic Acids Res, 2018, 46(D1): D152-D159  Goodarzi H, Liu X, Nguyen HCB, et al. Endogenous tRNA-Derived Fragments Suppress Breast Cancer Progression via YBX1 Displacement[J]. Cell, 2015, 161(4): 790-802  Schorn AJ, Gutbrod MJ, LeBlanc C, et al. LTR-Retrotransposon Control by tRNA-Derived Small RNAs [J]. Cell, 2017, 170(1): 61-71.e11  Kim HK, Fuchs G, Wang S, et al. A transfer-RNA-derived small RNA regulates ribosome biogenesis[J]. Nature, 2017, 552(7683): 57-62  Guzzi N, Cie?la M, Ngoc PCT, et al. Pseudouridylation of tRNA-Derived Fragments Steers Translational Control in Stem Cells[J]. Cell, 2018, 173(5): 1204-1216.e26  Ren B, Wang X, Duan J, et al. Rhizobial tRNA-derived small RNAs are signal molecules regulating plant nodulation[J]. Science, 2019, 365(6456): 919-922  Hardy D, Fefeu M, Besnard A, et al. Defective angiogenesis in CXCL12 mutant mice impairs skeletal muscle regeneration[J]. Skelet Muscle, 2019, 9(1): 25  Helmbacher F, Stricker S. Tissue cross talks governing limb muscle development and regeneration[J]. Semin Cell Dev Biol, 2020, 104: 14-30  Laurichesse Q, Soler C. Muscle development : a view from adult myogenesis in Drosophila[J]. Semin Cell Dev Biol, 2020, 104: 39-50  Jeong HJ, Lee SJ, Lee HJ, et al. Prmt7 promotes myoblast differentiation via methylation of p38MAPK on arginine residue 70[J]. Cell Death Differ, 2020, 27(2): 573-586  Tian H, Liu S, Ren J, et al. Role of Histone Deacetylases in Skeletal Muscle Physiology and Systemic Energy Homeostasis: Implications for Metabolic Diseases and Therapy[J]. Front Physiol, 2020, 11: 949  Chan RY, Boudreau-Larivière C, Angus LM, et al. An intronic enhancer containing an N-box motif is required for synapse- and tissue-specific expression of the acetylcholinesterase gene in skeletal muscle fibers[J]. Proc Natl Acad Sci U S A, 1999, 96(8): 4627-4632  Jeandard D, Smirnova A, Tarassov I, et al. Import of Non-Coding RNAs into Human Mitochondria: A Critical Review and Emerging Approaches[J]. Cells, 2019, 8(3): 286  Gan Z, Fu T, Kelly DP, et al. Skeletal muscle mitochondrial remodeling in exercise and diseases[J]. Cell Res, 2018, 28(10): 969-980  Herbst A, Pak JW, McKenzie D, et al. Accumulation of Mitochondrial DNA Deletion Mutations in Aged Muscle Fibers: Evidence for a Causal Role in Muscle Fiber Loss[J]. J Cerontol A Biol Sci Med Sci, 2007, 62(3): 235-245  Smits P, Smeitink J, van den Heuvel L. Mitochondrial translation and beyond: processes implicated in combined oxidative phosphorylation deficiencies[J]. J Biomed Biotechnol, 2010, 2010:737385  Schneider A. Mitochondrial tRNA import and its consequences for mitochondrial translation[J]. Annu Rev Biochem, 2011, 80: 1033-1053  Kimura S, Dedon PC, Waldor MK. Comparative tRNA sequencing and RNA mass spectrometry for surveying tRNA modifications[J]. Nat Chem Biol, 2020, 16(9): 964-972  Ehrenhofer-Murray AE. Cross-Talk between Dnmt2-Dependent tRNA Methylation and Queuosine Modification[J]. Biomolecules, 2017, 7(1): 14  Wang X, Matuszek Z, Huang Y, et al. Queuosine modification protects cognate tRNAs against ribonuclease cleavage[J]. RNA, 2018, 24(10): 1305-1313  Asano K, Suzuki T, Saito A, et al. Metabolic and chemical regulation of tRNA modification associated with taurine deficiency and human disease[J]. Nucleic Acids Res, 2018, 46(4): 1565-1583  Riley LG, Cooper S, Hickey P, et al. Mutation of the mitochondrial tyrosyl-tRNA synthetase gene, YARS2, causes myopathy, lactic acidosis, and sideroblastic anemia--MLASA syndrome[J]. Am J Hum Genet, 2010, 87(1): 52-59  Sato Y, Sato Y, Suzuki R, et al. Leucyl-tRNA synthetase is required for the myogenic differentiation of C2C12 myoblasts, but not for hypertrophy or metabolic alteration of myotubes[J]. Exp Cell Res, 2018, 364 (2): 184-190  Wittenhagen LM, Kelley SO. Dimerization of a pathogenic human mitochondrial tRNA[J]. Nat Struct Mol Biol, 2002, 9(8): 586-590  Kirino Y, Yasukawa T, Ohta S, et al. Codon-specific translational defect caused by a wobble modification deficiency in mutant tRNA from a human mitochondrial disease[J]. Proc Natl Acad Sci U S A, 2004, 101 (42): 15070-15075  Smits P, Mattijssen S, Morava E, et al. Functional consequences of mitochondrial tRNA Trp and tRNA Arg mutations causing combined OXPHOS defects[J]. Eur J Hum Genet, 2010, 18(3): 324-329  Shoffner JM, Lott MT, Lezza AM, et al. Myoclonic epilepsy and ragged-red fiber disease (MERRF) is associated with a mitochondrial DNA tRNA(Lys) mutation[J]. Cell, 1990, 61(6): 931-937  Souilem S, Chebel S,Mancuso M,et al.. A novel mitochondrial tRNA(Ile) point mutation associated with chronic progressive external ophthalmoplegia and hyperCKemia[J]. J Neurol Sci, 2011, 300(1-2): 187-190  Jones CN, Jones CI, Graham WD, et al. A disease-causing point mutation in human mitochondrial tRNAMet rsults in tRNA misfolding leading to defects in translational initiation and elongation[J]. J Biol Chem, 2008, 283(49): 34445-34456  Sacconi S, Salviati L, Gooch C, et al. Complex neurologic syndrome associated with the G1606A mutation of mitochondrial DNA[J]. Arch Neurol, 2002, 59(6): 1013-1015  McFarland R, Clark KM, Morris AAM, et al. Multiple neonatal deaths due to a homoplasmic mitochondrial DNA mutation[J]. Nat Genet, 2002, 30(2): 145-146  Moraes CT, Ciacci F, Bonilla E, et al. A mitochondrial tRNA anticodon swap associated with a muscle disease[J]. Nat Genet, 1993, 4(3): 284-288  Bonnefond L, Frugier M, Touzé E, et al. Crystal structure of human mitochondrial tyrosyl-tRNA synthetase reveals common and idiosyncratic features[J]. Structure, 2007, 15(11): 1505-1516  Scheper GC, van der Klok T, van Andel RJ, et al. Mitochondrial aspartyl-tRNA synthetase deficiency causes leukoencephalopathy with brain stem and spinal cord involvement and lactate elevation[J]. Nat Genet, 2007, 39(4): 534-539  Yao P, Fox PL. Aminoacyl-tRNA synthetases in medicine and disease[J]. EMBO Mol Med, 2013, 5(3): 332-343  Sleigh JN, Grice SJ, Burgess RW, et al. Neuromuscular junction maturation defects precede impaired lower motor neuron connectivity in Charcot-Marie-Tooth type 2D mice[J]. Hum Mol Genet, 2014, 23(10): 2639-2650  Pierce SB, Chisholm KM, Lynch ED, et al. Mutations in mitochondrial histidyl tRNA synthetase HARS2 cause ovarian dysgenesis and sensorineural hearing loss of Perrault syndrome[J]. Proc Natl Acad Sci U S A, 2011, 108(16): 6543-6548  Tisdale MJ. Mechanisms of cancer cachexia[J]. Physiol Rev, 2009, 89(2): 381-410  Gordon BS, Kelleher AR, Kimball SR. Regulation of muscle protein synthesis and the effects of catabolic states[J]. Int J Biochem Cell Biol, 2013, 45(10): 2147-2157  Bonhoure N, Byrnes A, Moir RD,et al. Loss of the RNA polymerase III repressor MAF1 confers obesity resistance[J]. Genes Dev, 2015, 29(9): 934-947  Iiboshi Y, Papst PJ, Kawasome H, et al. Amino acid-dependent control of p70(s6k). Involvement of tRNA aminoacylation in the regulation[J]. J Biol Chem, 1999, 274(2): 1092-1099  Wolfe RR, Song J, Sun J, et al. Total aminoacyl-transfer RNA pool is greater in liver than muscle in rabbits [J]. J Nutr, 2007, 137(11): 2333-2338  Soares AR, Fernandes N, Reverendo M, et al. Conserved and highly expressed tRNA derived fragments in zebrafish[J]. BMC Mol Biol, 2015, 16: 22  Sork H, Corso G, Krjutskov K, et al. Heterogeneity and interplay of the extracellular vesicle small RNA transcriptome and proteome[J]. Sci Rep, 2018, 8(1): 10813  Hanada T, Weitzer S, Mair B, et al. CLP1 links tRNA metabolism to progressive motor-neuron loss[J]. Nature, 2013, 495(7442): 474-480