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.

Základní údaje

Originální název

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

Autoři

MARTINO, Fabiana (380 Itálie, domácí), Nandan Mysore VARADARAJAN (356 Indie, domácí), Ana Rubina PERESTRELO, Václav HEJRET (203 Česká republika, domácí), Helena DURIKOVA, Dragana VUKIĆ (688 Srbsko, domácí), Vladimir HORVATH, Francesca CAVALIERI, Frank CARUSO, Waleed S ALBIHLAL, Andre P GERBER, Mary Anne O'CONNELL (372 Irsko, domácí), Štěpánka VAŇÁČOVÁ (203 Česká republika, garant, domácí), Stefania PAGLIARI a Giancarlo FORTE

Vydání

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

Další údaje

Jazyk

angličtina

Typ výsledku

Článek v odborném periodiku

Obor

10601 Cell biology

Stát vydavatele

Spojené státy

Utajení

není předmětem státního či obchodního tajemství

Odkazy

URL

Impakt faktor

Impact factor: 17.100

Kód RIV

RIV/00216224:14740/22:00128822

Organizační jednotka

Středoevropský technologický institut

DOI

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

UT WoS

000892365400001

Klíčová slova anglicky

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

Štítky

14110513, CF BIOIT, CF CELLIM, CF GEN, podil, rivok

Příznaky

Mezinárodní význam, Recenzováno

Změněno: 31. 10. 2024 11:59, Ing. Marie Švancarová

Anotace

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.

Návaznosti

GA20-11101S, projekt VaV

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

Investor: Grantová agentura ČR, Elucidating the role of the RNA editing enzyme ADAR1 in novel biological pathways and determine its posttranslational regulation.

GA20-19617S, projekt VaV

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

Investor: Grantová agentura ČR, The molecular mechanisms of noncanonical 3' terminal RNA tailing and its role in the metabolism of coding and noncoding RNAs

LQ1601, projekt VaV

Název: CEITEC 2020 (Akronym: CEITEC2020)

Investor: Ministerstvo školství, mládeže a tělovýchovy ČR, CEITEC 2020

LTC18052, projekt VaV

Název: Integrativní studium molekulárních mechanismů epitranskriptomu savčích buněk

Investor: Ministerstvo školství, mládeže a tělovýchovy ČR, Integrativní studium molekulárních mechanismů epitranskriptomu savčích buněk, INTER-COST

90129, velká výzkumná infrastruktura

Název: Czech-BioImaging II

90132, velká výzkumná infrastruktura

Název: NCMG II

90250, velká výzkumná infrastruktura

Název: Czech-BioImaging 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 a 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, roč. 14, č. 672, s. 1-17. ISSN 1946-6234. Dostupné z: 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 a 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, roč.~14, č.~672, s.~1-17. ISSN~1946-6234. Dostupné z: https://dx.doi.org/10.1126/scitranslmed.abo5715.

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