MYOSLID is a novel serum response factor-dependent long noncoding RNA that amplifies the vascular smooth muscle differentiation program

Jinjing Zhao, Wei Zhang, Mingyan Lin, Wen Wu, Pengtao Jiang, Emiley Tou, Min Xue, Angelene Richards, David Jourd'heuil, Arif Asif, Deyou Zheng, Harold A. Singer, Joseph M. Miano, Xiaochun Long

Research output: Contribution to journalArticle

Abstract

Objective - 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. Approach and Results - 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. Conclusions - 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.

Original languageEnglish (US)
Pages (from-to)2088-2099
Number of pages12
JournalArteriosclerosis, thrombosis, and vascular biology
Volume36
Issue number10
DOIs
StatePublished - Oct 1 2016
Externally publishedYes

Fingerprint

Long Noncoding RNA
Serum Response Factor
Vascular Smooth Muscle
Smooth Muscle
Smooth Muscle Myocytes
Cell Differentiation
Transforming Growth Factors
myocardin
Transcription Factors
RNA Sequence Analysis
Stress Fibers
Arteriovenous Fistula

Keywords

  • long noncoding RNA
  • myocardin
  • phenotype
  • stress fiber
  • vascular smooth muscle

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

Cite this

MYOSLID is a novel serum response factor-dependent long noncoding RNA that amplifies the vascular smooth muscle differentiation program. / Zhao, Jinjing; Zhang, Wei; Lin, Mingyan; Wu, Wen; Jiang, Pengtao; Tou, Emiley; Xue, Min; Richards, Angelene; Jourd'heuil, David; Asif, Arif; Zheng, Deyou; Singer, Harold A.; Miano, Joseph M.; Long, Xiaochun.

In: Arteriosclerosis, thrombosis, and vascular biology, Vol. 36, No. 10, 01.10.2016, p. 2088-2099.

Research output: Contribution to journalArticle

Zhao, J, Zhang, W, Lin, M, Wu, W, Jiang, P, Tou, E, Xue, M, Richards, A, Jourd'heuil, D, Asif, A, Zheng, D, Singer, HA, Miano, JM & Long, X 2016, 'MYOSLID is a novel serum response factor-dependent long noncoding RNA that amplifies the vascular smooth muscle differentiation program', Arteriosclerosis, thrombosis, and vascular biology, vol. 36, no. 10, pp. 2088-2099. https://doi.org/10.1161/ATVBAHA.116.307879
Zhao, Jinjing ; Zhang, Wei ; Lin, Mingyan ; Wu, Wen ; Jiang, Pengtao ; Tou, Emiley ; Xue, Min ; Richards, Angelene ; Jourd'heuil, David ; Asif, Arif ; Zheng, Deyou ; Singer, Harold A. ; Miano, Joseph M. ; Long, Xiaochun. / MYOSLID is a novel serum response factor-dependent long noncoding RNA that amplifies the vascular smooth muscle differentiation program. In: Arteriosclerosis, thrombosis, and vascular biology. 2016 ; Vol. 36, No. 10. pp. 2088-2099.
@article{50ba2fb60c6046dab23dd53de8c9d100,
title = "MYOSLID is a novel serum response factor-dependent long noncoding RNA that amplifies the vascular smooth muscle differentiation program",
abstract = "Objective - 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. Approach and Results - 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. Conclusions - 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.",
keywords = "long noncoding RNA, myocardin, phenotype, stress fiber, vascular smooth muscle",
author = "Jinjing Zhao and Wei Zhang and Mingyan Lin and Wen Wu and Pengtao Jiang and Emiley Tou and Min Xue and Angelene Richards and David Jourd'heuil and Arif Asif and Deyou Zheng and Singer, {Harold A.} and Miano, {Joseph M.} and Xiaochun Long",
year = "2016",
month = "10",
day = "1",
doi = "10.1161/ATVBAHA.116.307879",
language = "English (US)",
volume = "36",
pages = "2088--2099",
journal = "Arteriosclerosis, Thrombosis, and Vascular Biology",
issn = "1079-5642",
publisher = "Lippincott Williams and Wilkins",
number = "10",

}

TY - JOUR

T1 - MYOSLID is a novel serum response factor-dependent long noncoding RNA that amplifies the vascular smooth muscle differentiation program

AU - Zhao, Jinjing

AU - Zhang, Wei

AU - Lin, Mingyan

AU - Wu, Wen

AU - Jiang, Pengtao

AU - Tou, Emiley

AU - Xue, Min

AU - Richards, Angelene

AU - Jourd'heuil, David

AU - Asif, Arif

AU - Zheng, Deyou

AU - Singer, Harold A.

AU - Miano, Joseph M.

AU - Long, Xiaochun

PY - 2016/10/1

Y1 - 2016/10/1

N2 - Objective - 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. Approach and Results - 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. Conclusions - 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.

AB - Objective - 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. Approach and Results - 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. Conclusions - 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.

KW - long noncoding RNA

KW - myocardin

KW - phenotype

KW - stress fiber

KW - vascular smooth muscle

UR - http://www.scopus.com/inward/record.url?scp=84979708484&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84979708484&partnerID=8YFLogxK

U2 - 10.1161/ATVBAHA.116.307879

DO - 10.1161/ATVBAHA.116.307879

M3 - Article

C2 - 27444199

AN - SCOPUS:84979708484

VL - 36

SP - 2088

EP - 2099

JO - Arteriosclerosis, Thrombosis, and Vascular Biology

JF - Arteriosclerosis, Thrombosis, and Vascular Biology

SN - 1079-5642

IS - 10

ER -