Intranuclear cardiac troponin I plays a functional role in regulating Atp2a2 expression in cardiomyocytes

Qian Lu; Bo Pan; Haobo Bai; Weian Zhao; Lingjuan Liu; Gu Li; Ruimin Liu; Tiewei Lv; Xupei Huang; Xi Li; Jie Tian

doi:10.1016/j.gendis.2021.04.007

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Intranuclear cardiac troponin I plays a functional role in regulating Atp2a2 expression in cardiomyocytes

Full-length article | 更新时间：2022-11-09

- Intranuclear cardiac troponin I plays a functional role in regulating Atp2a2 expression in cardiomyocytes
- Intranuclear cardiac troponin I plays a functional role in regulating Atp2a2 expression in cardiomyocytes
- Genes & Diseases 2022年9卷第6期
- 作者机构：
  
  1. Department of Pediatric Cardiology, Ministry of Education Key Laboratory of Child Development and Disorders, National Clinical Research Center for Child Health and Disorders, China International Science and Technology Cooperation Base of Child Development and Critical Disorders, Children's Hospital of Chongqing Medical University,Chongqing,PR China,400014
  2. Chongqing Key Laboratory of Pediatrics,Chongqing,PR China,400014
  3. Department of Biomedical Science, Charlie E. Schmidt College of Medicine, Florida Atlantic University, Boca Raton,FL,USA,33431
  4. Department of Orthopedic, The First Affiliated Hospital of Chongqing Medical University,Chongqing,PR China,400016
  5. Biology Science Institutes of Chongqing Medical University,Chongqing,PR China,400016
- 作者简介：
- 基金信息：
- DOI：10.1016/j.gendis.2021.04.007
  中图分类号：
- 纸质出版日期：2022，
  
  网络出版日期：2022-11-1，
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Intranuclear cardiac troponin I plays a functional role in regulating Atp2a2 expression in cardiomyocytes[J]. Genes & Diseases, 2022,9(6).

Qian Lu, Bo Pan, Haobo Bai, et al. Intranuclear cardiac troponin I plays a functional role in regulating Atp2a2 expression in cardiomyocytes[J]. Genes & Diseases, 2022,9(6).
Intranuclear cardiac troponin I plays a functional role in regulating Atp2a2 expression in cardiomyocytes[J]. Genes & Diseases, 2022,9(6). DOI： 10.1016/j.gendis.2021.04.007.

Qian Lu, Bo Pan, Haobo Bai, et al. Intranuclear cardiac troponin I plays a functional role in regulating Atp2a2 expression in cardiomyocytes[J]. Genes & Diseases, 2022,9(6). DOI： 10.1016/j.gendis.2021.04.007.

摘要

Abstract

In the past studies

it is shown that cardiac troponin I (cTnI

encoded by

TNNI3

)

as a cytoplasmic protein

is an inhibitory subunit in troponin complex

and involves in cardiomyocyte diastolic regulation. Here

we assessed a novel role of cTnI as a nucleoprotein. Firstly

the nuclear translocation of cTnI was found in mouse

human fetuses and rat heart tissues. In addition

there were differences in percentage of intranuclear cTnI in different conditions. Based on weighted gene co-expression network analyses (WGCNA) and verification in cell experiments

a strong expression correlation was found between

TNNI3

and

Atp2a2

which encodes sarco-endoplasmic reticulum Ca

ATPase isoform 2a (SERCA2a)

and involves in ATP hydrolysis and Ca

transient. TNNI3 gain and loss caused Atpa2a2 increase/decrease in a dose-dependent manner both in mRNA and protein levels

in vivo

and

in vitro

. By using ChIP-sequence we demonstrated specific binding DNA sequences of cTnI were enriched in

ATP2a2

promoter −239∼–889 region and the specific binding sequence motif of cTnI was analyzed by software as "CCAT"

which has been reported to be required for

YY1

binding to the promoter region of

YY1

-related genes. Moreover

it was further verified that pcDNA3.1 (−)-TNNI3 could express cTnI proteins and increase the promoter activity of

Atp2a2

through luciferase report assay. In the end

we evaluated beat frequencies

total ATP contents

transients in

TNNI3

-siRNA myocardial cells. These findings indicated

for the first time

cTnI may regulate

Atp2a2

in cardiomyocytes as a co-regulatory factor and participate in the regulation of intracellular Ca ions.

关键词

Keywords

Atp2a2Ca ionsIntranuclear cardiac troponin INuclear translocationYY1

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