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@ARTICLE{Berulava:141698,
author = {Berulava, Tea and Buchholz, Eric and Elerdashvili, Vakhtang
and Pena Centeno, Tonatiuh and Islam, Rezaul and Lbik, Dawid
and Mohamed, Belal A and Renner, Andre and von Lewinski,
Dirk and Sacherer, Michael and Bohnsack, Katherine E and
Bohnsack, Markus T and Jain, Gaurav and Capece, Vincenzo and
Cleve, Nicole and Burkhardt, Susanne and Hasenfuss, Gerd and
Fischer, Andre and Toischer, Karl},
title = {{C}hanges in m6{A} {RNA} methylation contribute to heart
failure progression by modulating translation.},
journal = {European journal of heart failure},
volume = {22},
number = {1},
issn = {1388-9842},
address = {Oxford},
publisher = {Wiley},
reportid = {DZNE-2020-00029},
pages = {54-66},
year = {2020},
abstract = {Deregulation of epigenetic processes and aberrant gene
expression are important mechanisms in heart failure. Here
we studied the potential relevance of m6A RNA methylation in
heart failure development.We analysed m6A RNA methylation
via next-generation sequencing. We found that approximately
one quarter of the transcripts in the healthy mouse and
human heart exhibit m6A RNA methylation. During progression
to heart failure we observed that changes in m6A RNA
methylation exceed changes in gene expression both in mouse
and human. RNAs with altered m6A RNA methylation were mainly
linked to metabolic and regulatory pathways, while changes
in RNA expression level mainly represented changes in
structural plasticity. Mechanistically, we could link m6A
RNA methylation to altered RNA translation and protein
production. Interestingly, differentially methylated but not
differentially expressed RNAs showed differential polysomal
occupancy, indicating transcription-independent modulation
of translation. Furthermore, mice with a cardiomyocyte
restricted knockout of the RNA demethylase Fto exhibited an
impaired cardiac function compared to control mice.We could
show that m6A landscape is altered in heart hypertrophy and
heart failure. m6A RNA methylation changes lead to changes
in protein abundance, unconnected to mRNA levels. This
uncovers a new transcription-independent mechanisms of
translation regulation. Therefore, our data suggest that
modulation of epitranscriptomic processes such as m6A
methylation might be an interesting target for therapeutic
interventions.},
keywords = {Animals / Epigenesis, Genetic / Heart Failure: genetics /
Methylation / Mice / RNA: genetics / RNA: metabolism / RNA,
Messenger: genetics},
cin = {AG Fischer 1 ; AG Fischer / Göttingen common /
Bioinformatics and Genome Dynamics Core / AG Bonn 2 ; AG
Bonn 2 / RNAome database},
ddc = {610},
cid = {I:(DE-2719)1410002 / I:(DE-2719)6000014 /
I:(DE-2719)1440016 / I:(DE-2719)1440012 /
I:(DE-2719)1410004},
pnm = {342 - Disease Mechanisms and Model Systems (POF3-342)},
pid = {G:(DE-HGF)POF3-342},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:31849158},
doi = {10.1002/ejhf.1672},
url = {https://pub.dzne.de/record/141698},
}