title: MYOSLID Is a Novel Serum Response Factor-Dependent Long Noncoding RNA That Amplifies the Vascular Smooth Muscle Differentiation Program.
abstract: Long noncoding RNAs (lncRNA) represent a growing class of noncoding genes with diverse cellular functions. We previously reported on SENCR, an lncRNA that seems to support the vascular smooth muscle cell (VSMC) contractile phenotype. However, information about the VSMC-specific lncRNAs regulated by myocardin (MYOCD)/serum response factor, the master switch for VSMC differentiation, is unknown.
  
  
  
  To define novel lncRNAs with functions related to VSMC differentiation, we performed RNA sequencing in human coronary artery SMCs that overexpress MYOCD. Several novel lncRNAs showed altered expression with MYOCD overexpression and one, named MYOcardin-induced Smooth muscle LncRNA, Inducer of Differentiation (MYOSLID), was activated by MYOCD and selectively expressed in VSMCs. MYOSLID was a direct transcriptional target of both MYOCD/serum response factor and transforming growth factor-β/SMAD pathways. Functional studies revealed that MYOSLID promotes VSMC differentiation and inhibits VSMC proliferation. MYOSLID showed reduced expression in failed human arteriovenous fistula samples compared with healthy veins. Although MYOSLID did not affect gene expression of transcription factors, such as serum response factor and MYOCD, its depletion in VSMCs disrupted actin stress fiber formation and blocked nuclear translocation of MYOCD-related transcription factor A (MKL1). Finally, loss of MYOSLID abrogated transforming growth factor-β1-induced SMAD2 phosphorylation.
  
  
  
  We have demonstrated that MYOSLID, the first human VSMC-selective and serum response factor/CArG-dependent lncRNA, is a novel modulator in amplifying the VSMC differentiation program, likely through feed-forward actions of both MKL1 and transforming growth factor-β/SMAD pathways.
authors.affiliation: From the Department of Molecular and Cellular Physiology (J.Z., W.Z., W.W., E.T., M.X., A.R., D.J., H.A.S., X.L.), Albany Medical College, NY; Department of Medicine, Jersey Shore University Medical Center, Neptune, NJ (A.A.); Departments of Genetics (M.L., D.Z.) and Neurology and Neuroscience (D.Z.), Albert Einstein College of Medicine, Bronx, NY; Aab Cardiovascular Research Institute, University of Rochester School of Medicine and Dentistry, NY (P.J., J.M.M.); and National Aquafeed Safety Assessment Center, Feed Research Institute, Chinese Academy of Agricultural Sciences, Beijing, P.R. China (M.X.).
authors.forename: Jinjing
authors.initials: J
authors.lastname: Zhao
authors.affiliation: From the Department of Molecular and Cellular Physiology (J.Z., W.Z., W.W., E.T., M.X., A.R., D.J., H.A.S., X.L.), Albany Medical College, NY; Department of Medicine, Jersey Shore University Medical Center, Neptune, NJ (A.A.); Departments of Genetics (M.L., D.Z.) and Neurology and Neuroscience (D.Z.), Albert Einstein College of Medicine, Bronx, NY; Aab Cardiovascular Research Institute, University of Rochester School of Medicine and Dentistry, NY (P.J., J.M.M.); and National Aquafeed Safety Assessment Center, Feed Research Institute, Chinese Academy of Agricultural Sciences, Beijing, P.R. China (M.X.).
authors.forename: Wei
authors.initials: W
authors.lastname: Zhang
authors.affiliation: From the Department of Molecular and Cellular Physiology (J.Z., W.Z., W.W., E.T., M.X., A.R., D.J., H.A.S., X.L.), Albany Medical College, NY; Department of Medicine, Jersey Shore University Medical Center, Neptune, NJ (A.A.); Departments of Genetics (M.L., D.Z.) and Neurology and Neuroscience (D.Z.), Albert Einstein College of Medicine, Bronx, NY; Aab Cardiovascular Research Institute, University of Rochester School of Medicine and Dentistry, NY (P.J., J.M.M.); and National Aquafeed Safety Assessment Center, Feed Research Institute, Chinese Academy of Agricultural Sciences, Beijing, P.R. China (M.X.).
authors.forename: Mingyan
authors.initials: M
authors.lastname: Lin
authors.affiliation: From the Department of Molecular and Cellular Physiology (J.Z., W.Z., W.W., E.T., M.X., A.R., D.J., H.A.S., X.L.), Albany Medical College, NY; Department of Medicine, Jersey Shore University Medical Center, Neptune, NJ (A.A.); Departments of Genetics (M.L., D.Z.) and Neurology and Neuroscience (D.Z.), Albert Einstein College of Medicine, Bronx, NY; Aab Cardiovascular Research Institute, University of Rochester School of Medicine and Dentistry, NY (P.J., J.M.M.); and National Aquafeed Safety Assessment Center, Feed Research Institute, Chinese Academy of Agricultural Sciences, Beijing, P.R. China (M.X.).
authors.forename: Wen
authors.initials: W
authors.lastname: Wu
authors.affiliation: From the Department of Molecular and Cellular Physiology (J.Z., W.Z., W.W., E.T., M.X., A.R., D.J., H.A.S., X.L.), Albany Medical College, NY; Department of Medicine, Jersey Shore University Medical Center, Neptune, NJ (A.A.); Departments of Genetics (M.L., D.Z.) and Neurology and Neuroscience (D.Z.), Albert Einstein College of Medicine, Bronx, NY; Aab Cardiovascular Research Institute, University of Rochester School of Medicine and Dentistry, NY (P.J., J.M.M.); and National Aquafeed Safety Assessment Center, Feed Research Institute, Chinese Academy of Agricultural Sciences, Beijing, P.R. China (M.X.).
authors.forename: Pengtao
authors.initials: P
authors.lastname: Jiang
authors.affiliation: From the Department of Molecular and Cellular Physiology (J.Z., W.Z., W.W., E.T., M.X., A.R., D.J., H.A.S., X.L.), Albany Medical College, NY; Department of Medicine, Jersey Shore University Medical Center, Neptune, NJ (A.A.); Departments of Genetics (M.L., D.Z.) and Neurology and Neuroscience (D.Z.), Albert Einstein College of Medicine, Bronx, NY; Aab Cardiovascular Research Institute, University of Rochester School of Medicine and Dentistry, NY (P.J., J.M.M.); and National Aquafeed Safety Assessment Center, Feed Research Institute, Chinese Academy of Agricultural Sciences, Beijing, P.R. China (M.X.).
authors.forename: Emiley
authors.initials: E
authors.lastname: Tou
authors.affiliation: From the Department of Molecular and Cellular Physiology (J.Z., W.Z., W.W., E.T., M.X., A.R., D.J., H.A.S., X.L.), Albany Medical College, NY; Department of Medicine, Jersey Shore University Medical Center, Neptune, NJ (A.A.); Departments of Genetics (M.L., D.Z.) and Neurology and Neuroscience (D.Z.), Albert Einstein College of Medicine, Bronx, NY; Aab Cardiovascular Research Institute, University of Rochester School of Medicine and Dentistry, NY (P.J., J.M.M.); and National Aquafeed Safety Assessment Center, Feed Research Institute, Chinese Academy of Agricultural Sciences, Beijing, P.R. China (M.X.).
authors.forename: Min
authors.initials: M
authors.lastname: Xue
authors.affiliation: From the Department of Molecular and Cellular Physiology (J.Z., W.Z., W.W., E.T., M.X., A.R., D.J., H.A.S., X.L.), Albany Medical College, NY; Department of Medicine, Jersey Shore University Medical Center, Neptune, NJ (A.A.); Departments of Genetics (M.L., D.Z.) and Neurology and Neuroscience (D.Z.), Albert Einstein College of Medicine, Bronx, NY; Aab Cardiovascular Research Institute, University of Rochester School of Medicine and Dentistry, NY (P.J., J.M.M.); and National Aquafeed Safety Assessment Center, Feed Research Institute, Chinese Academy of Agricultural Sciences, Beijing, P.R. China (M.X.).
authors.forename: Angelene
authors.initials: A
authors.lastname: Richards
authors.affiliation: From the Department of Molecular and Cellular Physiology (J.Z., W.Z., W.W., E.T., M.X., A.R., D.J., H.A.S., X.L.), Albany Medical College, NY; Department of Medicine, Jersey Shore University Medical Center, Neptune, NJ (A.A.); Departments of Genetics (M.L., D.Z.) and Neurology and Neuroscience (D.Z.), Albert Einstein College of Medicine, Bronx, NY; Aab Cardiovascular Research Institute, University of Rochester School of Medicine and Dentistry, NY (P.J., J.M.M.); and National Aquafeed Safety Assessment Center, Feed Research Institute, Chinese Academy of Agricultural Sciences, Beijing, P.R. China (M.X.).
authors.forename: David
authors.initials: D
authors.lastname: Jourd'heuil
authors.affiliation: From the Department of Molecular and Cellular Physiology (J.Z., W.Z., W.W., E.T., M.X., A.R., D.J., H.A.S., X.L.), Albany Medical College, NY; Department of Medicine, Jersey Shore University Medical Center, Neptune, NJ (A.A.); Departments of Genetics (M.L., D.Z.) and Neurology and Neuroscience (D.Z.), Albert Einstein College of Medicine, Bronx, NY; Aab Cardiovascular Research Institute, University of Rochester School of Medicine and Dentistry, NY (P.J., J.M.M.); and National Aquafeed Safety Assessment Center, Feed Research Institute, Chinese Academy of Agricultural Sciences, Beijing, P.R. China (M.X.).
authors.forename: Arif
authors.initials: A
authors.lastname: Asif
authors.affiliation: From the Department of Molecular and Cellular Physiology (J.Z., W.Z., W.W., E.T., M.X., A.R., D.J., H.A.S., X.L.), Albany Medical College, NY; Department of Medicine, Jersey Shore University Medical Center, Neptune, NJ (A.A.); Departments of Genetics (M.L., D.Z.) and Neurology and Neuroscience (D.Z.), Albert Einstein College of Medicine, Bronx, NY; Aab Cardiovascular Research Institute, University of Rochester School of Medicine and Dentistry, NY (P.J., J.M.M.); and National Aquafeed Safety Assessment Center, Feed Research Institute, Chinese Academy of Agricultural Sciences, Beijing, P.R. China (M.X.).
authors.forename: Deyou
authors.initials: D
authors.lastname: Zheng
authors.affiliation: From the Department of Molecular and Cellular Physiology (J.Z., W.Z., W.W., E.T., M.X., A.R., D.J., H.A.S., X.L.), Albany Medical College, NY; Department of Medicine, Jersey Shore University Medical Center, Neptune, NJ (A.A.); Departments of Genetics (M.L., D.Z.) and Neurology and Neuroscience (D.Z.), Albert Einstein College of Medicine, Bronx, NY; Aab Cardiovascular Research Institute, University of Rochester School of Medicine and Dentistry, NY (P.J., J.M.M.); and National Aquafeed Safety Assessment Center, Feed Research Institute, Chinese Academy of Agricultural Sciences, Beijing, P.R. China (M.X.).
authors.forename: Harold A
authors.initials: HA
authors.lastname: Singer
authors.affiliation: From the Department of Molecular and Cellular Physiology (J.Z., W.Z., W.W., E.T., M.X., A.R., D.J., H.A.S., X.L.), Albany Medical College, NY; Department of Medicine, Jersey Shore University Medical Center, Neptune, NJ (A.A.); Departments of Genetics (M.L., D.Z.) and Neurology and Neuroscience (D.Z.), Albert Einstein College of Medicine, Bronx, NY; Aab Cardiovascular Research Institute, University of Rochester School of Medicine and Dentistry, NY (P.J., J.M.M.); and National Aquafeed Safety Assessment Center, Feed Research Institute, Chinese Academy of Agricultural Sciences, Beijing, P.R. China (M.X.).
authors.forename: Joseph M
authors.initials: JM
authors.lastname: Miano
authors.affiliation: From the Department of Molecular and Cellular Physiology (J.Z., W.Z., W.W., E.T., M.X., A.R., D.J., H.A.S., X.L.), Albany Medical College, NY; Department of Medicine, Jersey Shore University Medical Center, Neptune, NJ (A.A.); Departments of Genetics (M.L., D.Z.) and Neurology and Neuroscience (D.Z.), Albert Einstein College of Medicine, Bronx, NY; Aab Cardiovascular Research Institute, University of Rochester School of Medicine and Dentistry, NY (P.J., J.M.M.); and National Aquafeed Safety Assessment Center, Feed Research Institute, Chinese Academy of Agricultural Sciences, Beijing, P.R. China (M.X.). longx@mail.amc.edu.
authors.forename: Xiaochun
authors.initials: X
authors.lastname: Long
mesh_terms: D021581:Active Transport, Cell Nucleus; D001166:Arteriovenous Shunt, Surgical; D002454:Cell Differentiation; D049109:Cell Proliferation; D002478:Cells, Cultured; D003331:Coronary Vessels / Q000378:metabolism; D005786:Gene Expression Regulation; D061307:Human Umbilical Vein Endothelial Cells / Q000378:metabolism; D006801:Humans; D024510:Muscle Development; D009131:Muscle, Smooth, Vascular / Q000378:metabolism*; D032389:Myocytes, Smooth Muscle / Q000378:metabolism*; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D010641:Phenotype; D010766:Phosphorylation; D062085:RNA, Long Noncoding / Q000235:genetics / Q000378:metabolism*; D026362:Serum Response Factor / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D051899:Smad2 Protein / Q000378:metabolism; D022502:Stress Fibers / Q000378:metabolism; D013997:Time Factors; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic; D014162:Transfection; D053773:Transforming Growth Factor beta1 / Q000378:metabolism; D014661:Vasoconstriction; D000099251:Myocardin
chemical_list: D009687:Nuclear Proteins; D062085:RNA, Long Noncoding; D026362:Serum Response Factor; D051899:Smad2 Protein; D015534:Trans-Activators; D053773:Transforming Growth Factor beta1; D000099251:Myocardin; C431575:MRTFA protein, human; C497782:SMAD2 protein, human; C508960:TGFB1 protein, human; C000620300:long non-coding RNA MYOSLID, human
keywords: long noncoding RNA; myocardin; phenotype; stress fiber; vascular smooth muscle