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MicroRNA expression data from a heterozygous Titin-deficient mouse model and wildtype controls

ABSTRACT: Mutations in the sarcomeric protein titin are a major cause of human dilated cardiomyopathy. We have developed a knock-in mouse model that imitated a previously identified titin truncation mutation. The heterotygous Ttn-deficient mice develop features of DCM and therefore recapitulate the human phenotype. To investigate the role of microRNAs in titin-based heart failure, we performed a miRNA screen in heterozygous Ttn-deficient mice and their wildtype littermate controls.

ORGANISM(S): Mus musculus synthetic construct

PROVIDER: GSE90972 | GEO | 2017/01/31

SECONDARY ACCESSION(S): PRJNA356509

REPOSITORIES: GEO

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Depletion of m6A reader protein YTHDC1 induces dilated cardiomyopathy by abnormal splicing of Titin

Project description:N6-methyladenosine (m6A) is the most common internal modification in eukaryotic messenger RNAs (mRNAs) and plays essential roles in mammals. The function of this chemical modification is deciphered by m6A-specific binding proteins of the YTH family. Recent studies indicated that m6A methyltransferase METTL3 ('writer') and demethylase FTO ('eraser') play critical roles in cardiovascular diseases. However, function of m6A 'reader' proteins in the heart is still largely unknown. Here, we report that cardiac-speciﬁc ablation of Ythdc1 in postnatal heart exhibits progressive dilated cardiomyopathy, heart failure and dramatically increases the incidence of postnatal lethality. Mechanically, the transcript of Titin-the major DCM and heart failure related gene-is decorated by m6A modification and directly recognized by YTHDC1, deficiency of Ythdc1 in heart results in abnormal splicing of TTN and disarray of sarcomeric structures in the cardiomyocytes subsequently. Collectively, we demonstrated that YTHDC1-dependent TTN splicing is crucial for the postnatal heart development and cardiac function, which probably provides a potential target for treating DCM through tuning m6A modification of TTN mRNA.

2022-08-01 | GSE164353 | GEO

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Regulation of sarcomere formation and function in the healthy heart requires a titin intronic enhancer [ATAC-seq]

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Regulation of sarcomere formation and function in the healthy heart requires a titin intronic enhancer [scRNA-Seq]

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The Skeletal Muscle Molecular Clock Regulates Sarcomere Length Through Titin Splicing [2]

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The Skeletal Muscle Molecular Clock Regulates Sarcomere Length Through Titin Splicing [1]

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Truncated titin detection in TTNtv positive DCM human myocardium via patient and allele specific proteomics.

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2021-10-27 | MSV000088275 | MassIVE

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