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Klaus-Tschira-Institute für Computational Cardiology -
Abteilung Bioinformatik und Systemkardiologie

PostDoc Start-up Grants awarded

Congratulation to Tobias Jakobi, Heidelberg/Mannheim.

He received a PostDoc Start-up grant for:
"Investigating roles of dynamic RNA editing in the endoplasmic reticulum stress response in the heart"

Our book on circular RNAs is out (Springer Press)

Circular RNAs (series: Methods in Molecular Biology) has been published.
Editor: Christoph Dieterich & Argyris Papantonis

New team members

We welcome Mike Rightmire, Thiago Britto Borges and Etienne Boileau into our team.

New publication on circular RNAs in the heart

Identification of circular RNAs with host gene-independent expression in human model systems for cardiac differentiation and disease.

Siede D(1), Rapti K(2), Gorska AA(2), Katus HA(2), Altmüller J(3), Boeckel JN(2), Meder B(2), Maack C(4), Völkers M(2), Müller OJ(2), Backs J(5), Dieterich C(6).

AIMS: Cardiovascular disease, one of the most common causes of death in western populations, is characterized by changes in RNA splicing and expression. Circular RNAs (circRNA) originate from back-splicing events, which link a downstream 5′ splice site to an upstream 3′ splice site. Several back-splicing junctions (BSJ) have been described in heart biopsies from human, rat and mouse hearts (Werfel et al., 2016; Jakobi et al., 2016 ). Here, we use human induced pluripotent stem cell derived cardiomyocytes (hiPSC-CMs) to identify circRNA and host gene dynamics in cardiac development and disease. In parallel, we explore candidate interactions of selected homologs in mouse and rat via RIP-seq experiments.

METHODS AND RESULTS: Deep RNA sequencing of cardiomyocyte development and β-adrenergic stimulation uncovered 4518 circRNAs. The set of circular RNA host genes is enriched for chromatin modifiers and GTPase activity regulators. RNA-seq and qRT-PCR data showed that circular RNA expression is highly dynamic in the hiPSC-CM model with 320 circRNAs showing significant expression changes. Intriguingly, 82 circRNAs are independently regulated to their host genes. We validated the same circRNA dynamics for circRNAs from ATXN10, CHD7, DNAJC6 and SLC8A1 in biopsy material from human dilated cardiomyopathy (DCM) and control patients. Finally, we could show that rodent homologs of circMYOD, circSLC8A1, circATXN7 and circPHF21A interact with either the ribosome or Argonaute2 protein complexes.

CONCLUSION: CircRNAs are dynamically expressed in a hiPSC-CM model of cardiac development and stress response. Some circRNAs show similar, host-gene independent expression dynamics in patient samples and may interact with the ribosome and RISC complex. In summary, the hiPSC-CM model uncovered a new signature of potentially disease relevant circRNAs which may serve as novel therapeutic targets.

www.ncbi.nlm.nih.gov/pubmed/28676412

pulseR: Versatile computational analysis of RNA turnover from metabolic labeling experiments

Motivation:

High throughput sequencing machines can process many samples in a single run. For Illumina systems, sequencing reads are barcoded with an additional DNA tag that is contained in the respective sequencing adapters. The recognition of barcode and adapter sequences is hence commonly needed for the analysis of next generation sequencing data. Flexbar performs demultiplexing based on barcodes and adapter trimming for such data. read more…

 

 

Flexbar 3.0 – SIMD and multicore parallelization

Motivation:

High throughput sequencing machines can process many samples in a single run. For Illumina systems, sequencing reads are barcoded with an additional DNA tag that is contained in the respective sequencing adapters. The recognition of barcode and adapter sequences is hence commonly needed for the analysis of next generation sequencing data. Flexbar performs demultiplexing based on barcodes and adapter trimming for such data. read more…

A microRNA-129-5p/Rbfox crosstalk coordinates homeostatic downscaling of excitatory synapses – New paper

Abstract: Synaptic downscaling is a homeostatic mechanism that allows neurons to reduce firing rates during chronically elevated network activity. Although synaptic downscaling is important in neural circuit development and epilepsy, the underlying mechanisms are poorly described. We performed small RNA profiling in picrotoxin (PTX)-treated hippocampal neurons, a model of synaptic downscaling. Thereby, we identified eight microRNAs (miRNAs) that were increased in response to PTX, including miR-129-5p, whose inhibition blocked synaptic downscaling in vitro and reduced epileptic seizure severity in vivo Using transcriptome, proteome, and bioinformatic analysis, we identified the calcium pump Atp2b4 and doublecortin (Dcx) as miR-129-5p targets. Restoring Atp2b4 and Dcx expression was sufficient to prevent synaptic downscaling in PTX-treated neurons. Furthermore, we characterized a functional crosstalk between miR-129-5p and the RNA-binding protein (RBP) Rbfox1. In the absence of PTX, Rbfox1 promoted the expression of Atp2b4 and Dcx. Upon PTX treatment, Rbfox1 expression was downregulated by miR-129-5p, thereby allowing the repression of Atp2b4 and Dcx. We therefore identified a novel activity-dependent miRNA/RBP crosstalk during synaptic scaling, with potential implications for neural network homeostasis and epileptogenesis.

Find me on Pubmed: https://www.ncbi.nlm.nih.gov/pubmed/28487411

 

 

Great Gordon Research Conference on RNA editing

One week of beautiful RNA modification science in Ventura / California.

Rp-bp is published in NAR

[Translate to English:] Wir haben eine weitere Publikation zur Identifizierung von translatierten RNA-Regionen aus Ribosom-Fußdruckdaten in Nucleic Acids Research.

Hier finden Sie alle weiteren Details: https://www.ncbi.nlm.nih.gov/pubmed/28126919

JACUSA is accepted for publication

JACUSA: Site-specific identification of RNA editing events from replicate sequencing data

 

https://www.ncbi.nlm.nih.gov/pubmed/28049429

Two new publications are out

Somatic increase of CCT8 mimics proteostasis of human pluripotent stem cells and extends C. elegans lifespan.

Noormohammadi A, Khodakarami A, Gutierrez-Garcia R, Lee HJ, Koyuncu S, König T, Schindler C, Saez I, Fatima A, Dieterich C, Vilchez D.

Nat Commun. 2016 Nov 28;7:13649. doi: 10.1038/ncomms13649.

PMID: 27892468

Reducing RBM20 activity improves diastolic dysfunction and cardiac atrophy.

Hinze F, Dieterich C, Radke MH, Granzier H, Gotthardt M.

J Mol Med (Berl). 2016 Nov 26. [Epub ahead of print]

PMID: 27889803

Our team extended

We welcome Ralf Hauenschild and Parisa Rezaee Borj into our team!

New publication

Ivan Kel; Zisong Chang; Nadia Galluccio; Margherita Romeo; Stefano Beretta; Luisa Diomede; Alessandra Mezzelani; Luciano Milanesi; Christoph Dieterich; Ivan Merelli. SPIRE, a modular pipeline for eQTL analysis of RNA-Seq data, reveals a regulatory hotspot controlling miRNA expression in C. elegans

Our new team

We welcome Amit Sing and Aleksei Uvarovskii into our team!

Talk at GCB 2016 in Berlin

Our software contribution

FUCHS – Towards full circular RNA characterization using RNAseq

has been selected for a talk at GCB2016

You will find a preprint at https://peerj.com/preprints/2418/

New publication

Le HQ, Ghatak S, Yeung CC, Tellkamp F,Günschmann C, Dieterich C, Yeroslaviz A, Habermann B, Pombo A, Niessen CM, Wickström SA.
Mechanical regulation of transcription controls Polycomb-mediated gene silencing during lineage commitment.

Compute Cluster

Our compute cluster ready for operation.

Mondo complexes regulate TFEB via TOR inhibition to promote longevity in response to gonadal signals

Title: Mondo complexes regulate TFEB via TOR inhibition to promote longevity in response to gonadal signals

Authors: Shuhei Nakamura, Özlem Karalay, Philipp S. Jäger, MakotoHorikawa, Corinna Klein, Kayo Nakamura, Christian Latza, Sven E. Templer, Christoph Dieterich & Adam Antebi

Joint work with our dear colleagues from the MPI-AGE was accepted for publication
in Nature Communications.

New Compute Cluster is ordered

Our new compute cluster is ordered and we are eagerly awaiting our Christmas gift.

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