The mechanical regulation of RNA binding protein hnRNPC in the
failing heart

J 2022

The mechanical regulation of RNA binding protein hnRNPC in the failing heart

MARTINO, Fabiana, Nandan Mysore VARADARAJAN, Ana Rubina PERESTRELO, Václav HEJRET, Helena DURIKOVA et. al.

Basic information

Original name

The mechanical regulation of RNA binding protein hnRNPC in the failing heart

Authors

MARTINO, Fabiana (380 Italy, belonging to the institution), Nandan Mysore VARADARAJAN (356 India, belonging to the institution), Ana Rubina PERESTRELO, Václav HEJRET (203 Czech Republic, belonging to the institution), Helena DURIKOVA, Dragana VUKIĆ (688 Serbia, belonging to the institution), Vladimir HORVATH, Francesca CAVALIERI, Frank CARUSO, Waleed S ALBIHLAL, Andre P GERBER, Mary Anne O'CONNELL (372 Ireland, belonging to the institution), Štěpánka VAŇÁČOVÁ (203 Czech Republic, guarantor, belonging to the institution), Stefania PAGLIARI and Giancarlo FORTE

Edition

Science Translational Medicine, Washington, American Association for the Advancement of Science, 2022, 1946-6234

Other information

Language

English

Type of outcome

Článek v odborném periodiku

Field of Study

10601 Cell biology

Country of publisher

United States of America

Confidentiality degree

není předmětem státního či obchodního tajemství

References:

URL

Impact factor

Impact factor: 17.100

RIV identification code

RIV/00216224:14740/22:00128822

Organization unit

Central European Institute of Technology

DOI

http://dx.doi.org/10.1126/scitranslmed.abo5715

UT WoS

000892365400001

Keywords in English

Extracellular Matrix; Heart Failure; Heterogeneous-Nuclear Ribonucleoprotein Group C; Humans

Abstract

V originále

Cardiac pathologies are characterized by intense remodeling of the extracellular matrix (ECM) that eventually leads to heart failure. Cardiomyocytes respond to the ensuing biomechanical stress by reexpressing fetal contractile proteins via transcriptional and posttranscriptional processes, such as alternative splicing (AS). Here, we demonstrate that the heterogeneous nuclear ribonucleoprotein C (hnRNPC) is up-regulated and relocates to the sarcomeric Z-disc upon ECM pathological remodeling. We show that this is an active site of localized translation, where the ribonucleoprotein associates with the translation machinery. Alterations in hnRNPC expression, phosphorylation, and localization can be mechanically determined and affect the AS of mRNAs involved in mechanotransduction and cardiovascular diseases, including Hippo pathway effector Yes-associated protein 1. We propose that cardiac ECM remodeling serves as a switch in RNA metabolism by affecting an associated regulatory protein of the spliceosome apparatus. These findings offer new insights on the mechanism of mRNA homeostatic mechanoregulation in pathological conditions.

Links

GA20-11101S, research and development project

Name: Objasnění úlohy RNA-editačního enzymu ADAR1 v nových biologických drahách a určení jeho postranslační regulace.

Investor: Czech Science Foundation

GA20-19617S, research and development project

Name: Molekulární mechanismy nekanonických 3' terminálních modifikací RNA a jejich úloha v metabolismu kódujících a nekódujících RNA

Investor: Czech Science Foundation

LQ1601, research and development project

Name: CEITEC 2020 (Acronym: CEITEC2020)

Investor: Ministry of Education, Youth and Sports of the CR

LTC18052, research and development project

Name: Integrativní studium molekulárních mechanismů epitranskriptomu savčích buněk

Investor: Ministry of Education, Youth and Sports of the CR, Integrative studies of molecular mechanisms of mammalian epitranscriptome, INTER-COST

90129, large research infrastructures

Name: Czech-BioImaging II

90132, large research infrastructures

Name: NCMG II

90250, large research infrastructures

Name: Czech-BioImaging III

90267, large research infrastructures

Name: NCMG III

Citovat

MARTINO, Fabiana, Nandan Mysore VARADARAJAN, Ana Rubina PERESTRELO, Václav HEJRET, Helena DURIKOVA, Dragana VUKIĆ, Vladimir HORVATH, Francesca CAVALIERI, Frank CARUSO, Waleed S ALBIHLAL, Andre P GERBER, Mary Anne O'CONNELL, Štěpánka VAŇÁČOVÁ, Stefania PAGLIARI and Giancarlo FORTE. The mechanical regulation of RNA binding protein hnRNPC in the failing heart. Science Translational Medicine. Washington: American Association for the Advancement of Science, 2022, vol. 14, No 672, p. 1-17. ISSN 1946-6234. Available from: https://dx.doi.org/10.1126/scitranslmed.abo5715.

@article{2265424,
   author = {Martino, Fabiana and Varadarajan, Nandan Mysore and Perestrelo, Ana Rubina and Hejret, Václav and Durikova, Helena and Vukić, Dragana and Horvath, Vladimir and Cavalieri, Francesca and Caruso, Frank and Albihlal, Waleed S and Gerber, Andre P and O'Connell, Mary Anne and Vaňáčová, Štěpánka and Pagliari, Stefania and Forte, Giancarlo},
   article_location = {Washington},
   article_number = {672},
   doi = {http://dx.doi.org/10.1126/scitranslmed.abo5715},
   keywords = {Extracellular Matrix; Heart Failure; Heterogeneous-Nuclear Ribonucleoprotein Group C; Humans},
   language = {eng},
   issn = {1946-6234},
   journal = {Science Translational Medicine},
   title = {The mechanical regulation of RNA binding protein hnRNPC in the failing heart},
   url = {https://www.science.org/doi/10.1126/scitranslmed.abo5715},
   volume = {14},
   year = {2022}
}

TY  - JOUR
ID  - 2265424
AU  - Martino, Fabiana - Varadarajan, Nandan Mysore - Perestrelo, Ana Rubina - Hejret, Václav - Durikova, Helena - Vukić, Dragana - Horvath, Vladimir - Cavalieri, Francesca - Caruso, Frank - Albihlal, Waleed S - Gerber, Andre P - O'Connell, Mary Anne - Vaňáčová, Štěpánka - Pagliari, Stefania - Forte, Giancarlo
PY  - 2022
TI  - The mechanical regulation of RNA binding protein hnRNPC in the failing heart
JF  - Science Translational Medicine
VL  - 14
IS  - 672
SP  - 1-17
EP  - 1-17
PB  - American Association for the Advancement of Science
SN  - 19466234
KW  - Extracellular Matrix
KW  - Heart Failure
KW  - Heterogeneous-Nuclear Ribonucleoprotein Group C
KW  - Humans
UR  - https://www.science.org/doi/10.1126/scitranslmed.abo5715
N2  - Cardiac pathologies are characterized by intense remodeling of the extracellular matrix (ECM) that eventually leads to heart failure. Cardiomyocytes respond to the ensuing biomechanical stress by reexpressing fetal contractile proteins via transcriptional and posttranscriptional processes, such as alternative splicing (AS). Here, we demonstrate that the heterogeneous nuclear ribonucleoprotein C (hnRNPC) is up-regulated and relocates to the sarcomeric Z-disc upon ECM pathological remodeling. We show that this is an active site of localized translation, where the ribonucleoprotein associates with the translation machinery. Alterations in hnRNPC expression, phosphorylation, and localization can be mechanically determined and affect the AS of mRNAs involved in mechanotransduction and cardiovascular diseases, including Hippo pathway effector Yes-associated protein 1. We propose that cardiac ECM remodeling serves as a switch in RNA metabolism by affecting an associated regulatory protein of the spliceosome apparatus. These findings offer new insights on the mechanism of mRNA homeostatic mechanoregulation in pathological conditions.
ER  -

MARTINO, Fabiana, Nandan Mysore VARADARAJAN, Ana Rubina PERESTRELO, Václav HEJRET, Helena DURIKOVA, Dragana VUKI$\backslash$'C, Vladimir HORVATH, Francesca CAVALIERI, Frank CARUSO, Waleed S ALBIHLAL, Andre P GERBER, Mary Anne O'CONNELL, Štěpánka VAŇÁČOVÁ, Stefania PAGLIARI and Giancarlo FORTE. The mechanical regulation of RNA binding protein hnRNPC in the failing heart. \textit{Science Translational Medicine}. Washington: American Association for the Advancement of Science, 2022, vol.~14, No~672, p.~1-17. ISSN~1946-6234. Available from: https://dx.doi.org/10.1126/scitranslmed.abo5715.

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