Improving livestock and poultry growth rates and increasing meat production are urgently needed worldwide. Previously, we produced a myostatin (MSTN) and fibroblast growth factor 5 (FGF5) double-knockout (MF−/−) sheep by CRISPR Cas9 system to improve meat production, and also wool production. Both MF−/− sheep and the F1 generation (MF+/−) sheep showed an obvious “double-muscle” phenotype. In this study, we identified the expression profiles of long noncoding RNAs (lncRNAs) in wild-type and MF+/− sheep, then screened out the key candidate lncRNAs that can regulate myogenic differentiation and skeletal muscle development. These key candidate lncRNAs can serve as critical gatekeepers for muscle contraction, calcium ion transport and skeletal muscle cell differentiation, apoptosis, autophagy, and skeletal muscle inflammation, further revealing that lncRNAs play crucial roles in regulating muscle phenotype in MF+/− sheep. In conclusion, our newly identified lncRNAs may emerge as novel molecules for muscle development or muscle disease and provide a new reference for MSTN-mediated regulation of skeletal muscle development.
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References
1.
AmiroucheA, DurieuxAC, BanzetS, et al.Down-regulation of Akt/mammalian target of rapamycin signaling pathway in response to myostatin overexpression in skeletal muscle. Endocrinology, 2009; 150(1):286–294; doi: 10.1210/en.2008-0959
2.
BakhtiarizadehMR, HosseinpourB, ArefnezhadB, et al.In silico prediction of long intergenic non-coding RNAs in sheep. Genome, 2016; 59(4):263–275; doi: 10.1139/gen-2015-0141
3.
BakhtiarizadehMR, SalamiSA. Identification and Expression Analysis of Long Noncoding RNAs in Fat-Tail of Sheep Breeds. G3 (Bethesda), 2019; 9(4):1263–1276; doi: 10.1534/g3.118.201014
4.
BeanC, SalamonM, RaffaelloA, et al.The Ankrd2, Cdkn1c and calcyclin genes are under the control of MyoD during myogenic differentiation. J Mol Biol, 2005; 349(2):349–366; doi: 10.1016/j.jmb.2005.03.063
5.
Blin-WakkachC, LezotF, Ghoul-MazgarS, et al.Endogenous Msx1 antisense transcript: in vivo and in vitro evidences, structure, and potential involvement in skeleton development in mammals. Proc Natl Acad Sci U S A, 2001; 98(13):7336–7341; doi: 10.1073/pnas.131497098
6.
BolgerAM, LohseM, UsadelB. Trimmomatic: A flexible trimmer for Illumina sequence data. Bioinformatics, 2014; 30(15):2114–2120; doi: 10.1093/bioinformatics/btu170
7.
BuckinghamM. Myogenic progenitor cells and skeletal myogenesis in vertebrates. Curr Opin Genet Dev, 2006; 16(5):525–532; doi: 10.1016/j.gde.2006.08.008
8.
ByeAJH, PugazhendhiD, WoodhouseS, et al.The RNA-binding proteins Zfp36l1 and Zfp36l2 act redundantly in myogenesis. Skelet Muscle, 2018; 8(1):37; doi: 10.1186/s13395-018-0183-9
9.
CabiliMN, TrapnellC, GoffL, et al.Integrative annotation of human large intergenic noncoding RNAs reveals global properties and specific subclasses. Genes Dev, 2011; 25(18):1915–1927; doi: 10.1101/gad.17446611
ChenM, LiX, ZhangX, et al.A novel long non-coding RNA, lncKBTBD10, involved in bovine skeletal muscle myogenesis. In Vitro Cell Dev Biol Anim, 2019; 55(1):25–35; doi: 10.1007/s11626-018-0306-y
12.
ChenM, ZhangL, GuoY, et al.A novel lncRNA promotes myogenesis of bovine skeletal muscle satellite cells via PFN1-RhoA/Rac1. J Cell Mol Med, 2021a; doi: 10.1111/jcmm.16427
13.
ChenMM, ZhaoYP, ZhaoY, et al.Regulation of Myostatin on the Growth and Development of Skeletal Muscle. Front Cell Dev Biol, 2021b;9:785712; doi: 10.3389/fcell.2021.785712
14.
FanZ, LiuZ, XuK, et al.Long-term, multidomain analyses to identify the breed and allelic effects in MSTN-edited pigs to overcome lameness and sustainably improve nutritional meat production. Sci China Life Sci, 2022; 65(2):362–375; doi: 10.1007/s11427-020-1927-9
15.
FengZ, TangZL, LiK, et al.Molecular characterization of the BTG2 and BTG3 genes in fetal muscle development of pigs. Gene, 2007; 403(1–2):170–177; doi: 10.1016/j.gene.2007.08.009
16.
GaoX, ChandraT, GrattonMO, et al.HES6 acts as a transcriptional repressor in myoblasts and can induce the myogenic differentiation program. J Cell Biol, 2001; 154(6):1161–1171; doi: 10.1083/jcb.200104058
17.
GuenzlPM, BarlowDP. Macro lncRNAs: A new layer of cis-regulatory information in the mammalian genome. RNA Biol, 2012; 9(6):731–741; doi: 10.4161/rna.19985
18.
HausburgMA, DolesJD, ClementSL, et al.Post-transcriptional regulation of satellite cell quiescence by TTP-mediated mRNA decay. Elife, 2015; 4:e03390; doi: 10.7554/eLife.03390
19.
JanduraA, KrauseHM. The New RNA World: Growing Evidence for Long Noncoding RNA Functionality. Trends Genet, 2017; 33(10):665–676; doi: 10.1016/j.tig.2017.08.002
20.
JouliaD, BernardiH, GarandelV, et al.Mechanisms involved in the inhibition of myoblast proliferation and differentiation by myostatin. Experimental cell research, 2003; 286(2):263–275
21.
KimD, LangmeadB, SalzbergSL. HISAT: A fast spliced aligner with low memory requirements. Nat Methods, 2015; 12(4):357–360; doi: 10.1038/nmeth.3317
22.
KoppF, MendellJT. Functional Classification and Experimental Dissection of Long Noncoding RNAs. Cell, 2018; 172(3):393–407; doi: 10.1016/j.cell.2018.01.011
23.
LangleyB, ThomasM, BishopA, et al.Myostatin inhibits myoblast differentiation by down-regulating MyoD expression. J Biol Chem, 2002; 277(51):49831–49840; doi: 10.1074/jbc.M204291200
24.
LiCY, LiX, LiuZ, et al.Identification and characterization of long non-coding RNA in prenatal and postnatal skeletal muscle of sheep. Genomics, 2019; 111(2):133–141; doi: 10.1016/j.ygeno.2018.01.009
25.
LiQ, LiuR, ZhaoH, et al.Identification and Characterization of Long Noncoding RNAs in Ovine Skeletal Muscle. Animals (Basel) 2018a;8(7); doi: 10.3390/ani8070127
26.
LiX, LiC, XuY, et al.Analysis of pituitary transcriptomics indicates that lncRNAs are involved in the regulation of sheep estrus. Funct Integr Genomics, 2020; 20(4):563–573; doi: 10.1007/s10142-020-00735-y
27.
LiY, ChenX, SunH, et al.Long non-coding RNAs in the regulation of skeletal myogenesis and muscle diseases. Cancer Lett, 2018b;417:58–64; doi: 10.1016/j.canlet.2017.12.015
28.
LiaoY, SmythGK, ShiW. featureCounts: An efficient general purpose program for assigning sequence reads to genomic features. Bioinformatics, 2014; 30(7):923–930; doi: 10.1093/bioinformatics/btt656
29.
LinNY, LinTY, YangWH, et al.Differential expression and functional analysis of the tristetraprolin family during early differentiation of 3T3-L1 preadipocytes. Int J Biol Sci, 2012; 8(5):761–777; doi: 10.7150/ijbs.4036
30.
LiuX, LuoD, ZhangJ, et al.Distribution and relative expression of vasoactive receptors on arteries. Sci Rep, 2020; 10(1):15383; doi: 10.1038/s41598-020-72352-5
31.
PerteaM, PerteaGM, AntonescuCM, et al.StringTie enables improved reconstruction of a transcriptome from RNA-seq reads. Nat Biotechnol, 2015; 33(3):290–295; doi: 10.1038/nbt.3122
32.
RenC, DengM, FanY, et al.Genome-Wide Analysis Reveals Extensive Changes in LncRNAs during Skeletal Muscle Development in Hu Sheep. Genes (Basel) 2017; 8(8); doi: 10.3390/genes8080191
33.
RussellJA, WalleyKR. Vasopressin and its immune effects in septic shock. J Innate Immun, 2010; 2(5):446–460; doi: 10.1159/000318531
34.
SadallahS, EkenC, MartinPJ, et al.Microparticles (ectosomes) shed by stored human platelets downregulate macrophages and modify the development of dendritic cells. J Immunol, 2011; 186(11):6543–6552; doi: 10.4049/jimmunol.1002788
35.
SartoriR, MilanG, PatronM, et al.Smad2 and 3 transcription factors control muscle mass in adulthood. Am J Physiol Cell Physiol, 2009; 296(6):C1248–C1257; doi: 10.1152/ajpcell.00104.2009
36.
SeijffersR, ZhangJ, MatthewsJC, et al.ATF3 expression improves motor function in the ALS mouse model by promoting motor neuron survival and retaining muscle innervation. Proc Natl Acad Sci U S A, 2014; 111(4):1622–1627; doi: 10.1073/pnas.1314826111
37.
Simionescu-BankstonA, KumarA. Noncoding RNAs in the regulation of skeletal muscle biology in health and disease. J Mol Med (Berl), 2016; 94(8):853–866; doi: 10.1007/s00109-016-1443-y
38.
SpillerMP, KambadurR, JeanplongF, et al.The myostatin gene is a downstream target gene of basic helix-loop-helix transcription factor MyoD. Molecular and cellular biology, 2002; 22(20):7066–7082.
39.
SunX, LiM, SunY, et al.The developmental transcriptome sequencing of bovine skeletal muscle reveals a long noncoding RNA, lncMD, promotes muscle differentiation by sponging miR-125b. Biochim Biophys Acta, 2016; 1863(11):2835–2845; doi: 10.1016/j.bbamcr.2016.08.014
40.
TaylorWE, BhasinS, ArtazaJ, et al.Myostatin inhibits cell proliferation and protein synthesis in C2C12 muscle cells. Am J Physiol Endocrinol Metab, 2001; 280(2):E221–E228; doi: 10.1152/ajpendo.2001.280.2.E221
41.
ThomasM, LangleyB, BerryC, et al.Myostatin, a negative regulator of muscle growth, functions by inhibiting myoblast proliferation. J Biol Chem, 2000; 275(51):40235–40243; doi: 10.1074/jbc.M004356200
42.
TrendelenburgAU, MeyerA, RohnerD, et al.Myostatin reduces Akt/TORC1/p70S6K signaling, inhibiting myoblast differentiation and myotube size. Am J Physiol Cell Physiol, 2009; 296(6):C1258–C1270; doi: 10.1152/ajpcell.00105.2009
43.
WangGQ, WangY, XiongY, et al.Sirt1 AS lncRNA interacts with its mRNA to inhibit muscle formation by attenuating function of miR-34a. Sci Rep, 2016; 6:21865; doi: 10.1038/srep21865
44.
WangL, ZhaoY, BaoX, et al.LncRNA Dum interacts with Dnmts to regulate Dppa2 expression during myogenic differentiation and muscle regeneration. Cell Res, 2015; 25(3):335–350; doi: 10.1038/cr.2015.21
45.
WeiC, WuM, WangC, et al.Long noncoding RNA Lnc-SEMT modulates IGF2 expression by sponging miR-125b to promote sheep muscle development and growth. Cell Physiol Biochem, 2018; 49(2):447–462; doi: 10.1159/000492979
46.
WeikardR, DemasiusW, KuehnC. Mining long noncoding RNA in livestock. Anim Genet, 2017; 48(1):3–18; doi: 10.1111/age.12493
47.
WuT, WangS, WangL, et al.Long noncoding RNA (lncRNA) CTTN-IT1 elevates skeletal muscle satellite cell proliferation and differentiation by acting as ceRNA for YAP1 through absorbing miR-29a in Hu Sheep. Front Genet, 2020; 11:843; doi: 10.3389/fgene.2020.00843
48.
YangDL, GanML, TanY, et al.[MiR-222-3small er, cyrillic regulates the proliferation and differentiation of C2C12 myoblasts by targeting BTG2]. Mol Biol (Mosk), 2019; 53(1):44–52; doi: 10.1134/S002689841901018X
49.
YuanC, ZhangK, YueY, et al.Analysis of dynamic and widespread lncRNA and miRNA expression in fetal sheep skeletal muscle. PeerJ, 2020; 8:e9957; doi: 10.7717/peerj.9957
50.
ZhangC, ChengN, QiaoB, et al.Age-related decline of interferon-gamma responses in macrophage impairs satellite cell proliferation and regeneration. J Cachexia Sarcopenia Muscle, 2020; 11(5):1291–1305; doi: 10.1002/jcsm.12584
51.
ZhangZ, ChenH, LuY, et al.LncRNA BC032020 suppresses the survival of human pancreatic ductal adenocarcinoma cells by targeting ZNF451. Int J Oncol, 2018; 52(4):1224–1234; doi: 10.3892/ijo.2018.4289
52.
ZhaoY, ChenM, LiY, et al.A 90-day safety study of meat from MSTN and FGF5 double-knockout sheep in wistar rats. Life (Basel), 2022; 12(2):204; doi: 10.3390/life12020204
53.
ZhaoY, ChenM, LianD, et al.Non-coding RNA regulates the myogenesis of skeletal muscle satellite cells, injury repair and diseases. Cells, 2019; 8(9):988; doi: 10.3390/cells8090988
54.
ZhaoY, LiH, FangS, et al.NONCODE 2016: An informative and valuable data source of long non-coding RNAs. Nucleic Acids Res, 2016; 44(D1):D203–D208; doi: 10.1093/nar/gkv1252
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