miR-1/133a clusters cooperatively specify the cardiomyogenic lineage by adjustment of myocardin levels during embryonic heart development.

miRNAs are small RNAs directing many developmental processes by posttranscriptional regulation of protein-coding genes. We uncovered a new role for miR-1-1/133a-2 and miR-1-2/133a-1 clusters in the specification of embryonic cardiomyocytes allowing transition from an immature state characterized by...

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Autores principales:	Katharina Wystub, Johannes Besser, Angela Bachmann, Thomas Boettger, Thomas Braun
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2013
Materias:	Genetics QH426-470
Acceso en línea:	https://doaj.org/article/e06a301d65e34143ac2e31323c246c5b
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spelling	oai:doaj.org-article:e06a301d65e34143ac2e31323c246c5b2021-11-18T06:21:51ZmiR-1/133a clusters cooperatively specify the cardiomyogenic lineage by adjustment of myocardin levels during embryonic heart development.1553-73901553-740410.1371/journal.pgen.1003793https://doaj.org/article/e06a301d65e34143ac2e31323c246c5b2013-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/24068960/?tool=EBIhttps://doaj.org/toc/1553-7390https://doaj.org/toc/1553-7404miRNAs are small RNAs directing many developmental processes by posttranscriptional regulation of protein-coding genes. We uncovered a new role for miR-1-1/133a-2 and miR-1-2/133a-1 clusters in the specification of embryonic cardiomyocytes allowing transition from an immature state characterized by expression of smooth muscle (SM) genes to a more mature fetal phenotype. Concomitant knockout of miR-1-1/133a-2 and miR-1-2/133a-1 released suppression of the transcriptional co-activator myocardin, a major regulator of SM gene expression, but not of its binding partner SRF. Overexpression of myocardin in the embryonic heart essentially recapitulated the miR-1/133a mutant phenotype at the molecular level, arresting embryonic cardiomyocytes in an immature state. Interestingly, the majority of postulated miR-1/133a targets was not altered in double mutant mice, indicating that the ability of miR-1/133a to suppress target molecules strongly depends on the cellular context. Finally, we show that myocardin positively regulates expression of miR-1/133a, thus constituting a negative feedback loop that is essential for early cardiac development.Katharina WystubJohannes BesserAngela BachmannThomas BoettgerThomas BraunPublic Library of Science (PLoS)articleGeneticsQH426-470ENPLoS Genetics, Vol 9, Iss 9, p e1003793 (2013)
institution	DOAJ
collection	DOAJ
language	EN
topic	Genetics QH426-470
spellingShingle	Genetics QH426-470 Katharina Wystub Johannes Besser Angela Bachmann Thomas Boettger Thomas Braun miR-1/133a clusters cooperatively specify the cardiomyogenic lineage by adjustment of myocardin levels during embryonic heart development.
description	miRNAs are small RNAs directing many developmental processes by posttranscriptional regulation of protein-coding genes. We uncovered a new role for miR-1-1/133a-2 and miR-1-2/133a-1 clusters in the specification of embryonic cardiomyocytes allowing transition from an immature state characterized by expression of smooth muscle (SM) genes to a more mature fetal phenotype. Concomitant knockout of miR-1-1/133a-2 and miR-1-2/133a-1 released suppression of the transcriptional co-activator myocardin, a major regulator of SM gene expression, but not of its binding partner SRF. Overexpression of myocardin in the embryonic heart essentially recapitulated the miR-1/133a mutant phenotype at the molecular level, arresting embryonic cardiomyocytes in an immature state. Interestingly, the majority of postulated miR-1/133a targets was not altered in double mutant mice, indicating that the ability of miR-1/133a to suppress target molecules strongly depends on the cellular context. Finally, we show that myocardin positively regulates expression of miR-1/133a, thus constituting a negative feedback loop that is essential for early cardiac development.
format	article
author	Katharina Wystub Johannes Besser Angela Bachmann Thomas Boettger Thomas Braun
author_facet	Katharina Wystub Johannes Besser Angela Bachmann Thomas Boettger Thomas Braun
author_sort	Katharina Wystub
title	miR-1/133a clusters cooperatively specify the cardiomyogenic lineage by adjustment of myocardin levels during embryonic heart development.
title_short	miR-1/133a clusters cooperatively specify the cardiomyogenic lineage by adjustment of myocardin levels during embryonic heart development.
title_full	miR-1/133a clusters cooperatively specify the cardiomyogenic lineage by adjustment of myocardin levels during embryonic heart development.
title_fullStr	miR-1/133a clusters cooperatively specify the cardiomyogenic lineage by adjustment of myocardin levels during embryonic heart development.
title_full_unstemmed	miR-1/133a clusters cooperatively specify the cardiomyogenic lineage by adjustment of myocardin levels during embryonic heart development.
title_sort	mir-1/133a clusters cooperatively specify the cardiomyogenic lineage by adjustment of myocardin levels during embryonic heart development.
publisher	Public Library of Science (PLoS)
publishDate	2013
url	https://doaj.org/article/e06a301d65e34143ac2e31323c246c5b
work_keys_str_mv	AT katharinawystub mir1133aclusterscooperativelyspecifythecardiomyogeniclineagebyadjustmentofmyocardinlevelsduringembryonicheartdevelopment AT johannesbesser mir1133aclusterscooperativelyspecifythecardiomyogeniclineagebyadjustmentofmyocardinlevelsduringembryonicheartdevelopment AT angelabachmann mir1133aclusterscooperativelyspecifythecardiomyogeniclineagebyadjustmentofmyocardinlevelsduringembryonicheartdevelopment AT thomasboettger mir1133aclusterscooperativelyspecifythecardiomyogeniclineagebyadjustmentofmyocardinlevelsduringembryonicheartdevelopment AT thomasbraun mir1133aclusterscooperativelyspecifythecardiomyogeniclineagebyadjustmentofmyocardinlevelsduringembryonicheartdevelopment
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miR-1/133a clusters cooperatively specify the cardiomyogenic lineage by adjustment of myocardin levels during embryonic heart development.

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