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Published: RNA Modification Level Estimation with pulseR

Posted on December 11, 2018 by

Abstract

RNA modifications regulate the complex life of transcripts. An experimental approach called LAIC-seq was developed to characterize modification levels on a transcriptome-wide scale. In this method, the modified and unmodified molecules are separated using antibodies specific for a given RNA modification (e.g., m6A). In essence, the procedure of biochemical separation yields three fractions: Input, eluate, and supernatent, which are subjected to RNA-seq. In this work, we present a bioinformatics workflow, which starts from RNA-seq data to infer gene-specific modification levels by a statistical model on a transcriptome-wide scale. Our workflow centers around the pulseR package, which was originally developed for the analysis of metabolic labeling experiments. We demonstrate how to analyze data without external normalization (i.e., in the absence of spike-ins), given high efficiency of separation, and how, alternatively, scaling factors can be derived from unmodified spike-ins. Importantly, our workflow provides an estimate of uncertainty of modification levels in terms of confidence intervals for model parameters, such as gene expression and RNA modification levels. We also compare alternative model parametrizations, log-odds, or the proportion of the modified molecules and discuss the pros and cons of each representation. In summary, our workflow is a versatile approach to RNA modification level estimation, which is open to any read-count-based experimental approach.

https://www.mdpi.com/2073-4425/9/12/619

Posted in Publications


Dieterich Lab is now a member of epitran.eu

Posted on December 5, 2018 by

We are now an official member of the Epitran network (check out: https://epitran.eu )

Posted in General


Accepted: A placental mammal-specific microRNA cluster acts as a natural brake for sociability in mice

Posted on November 26, 2018 by

Did you ever wonder how ncRNAs could influence behavior ?

Then, you would probably like to read on it in our new EMBO reports manuscript by

Lackinger, M., Sungur, A.Ö., Daswani, R., Soutschek, M., Bicker, S., Stemmler, L., Wüst, T., Fiore, R., Dieterich, C., Schwarting, R.K.W., Wöhr, M. and Schratt, G.

Aberrant synaptic function is thought to underlie social deficits in neurodevelopmental disorders such as autism and schizophrenia. microRNAs have been shown to regulate synapse development and plasticity, their potential involvement in the control of social behaviour in mammals however remains unexplored. Here we show that deletion of the large placental mammal-specific miR379-410 cluster in mice unexpectedly leads to hypersocial behaviour, which is accompanied by increased excitatory synaptic transmission and exaggerated expression of ionotropic glutamate receptor complexes in the hippocampus. Bioinformatics further allowed us to identify five “hub” microRNAs whose deletion accounts for a large part of the upregulation of excitatory synaptic genes, including Cnih2, Dlgap3, Prr7 and Src. Thus, miR379-410 is a natural brake for sociability and interfering with specific members of this cluster could represent a therapeutic strategy for social deficits in neurodevelopmental disorders.

Posted in General


CircTools manuscript accepted at Bioinformatics

Posted on November 16, 2018 by

circtools: a modular, python-based framework for circRNA-related tools that unifies several functionalities in a single, command line driven software has been accepted for publication in Bioinformatics.

Please visit https://github.com/dieterich-lab/circtools for more information.

Posted in Publications, Software


Methods for Analysis of Circular RNAs: No Tautology

Posted on October 24, 2018 by

We are excited to announce funding by EMBO for implementing a workshop on circular RNAs.

Organizers: Vladimir Benes (main), Irene Bozzoni, Marie-Laure Baudet and
Christoph Dieterich
Category: EMBO Practical Course
Title: EMBO Practical Course: Methods for analysis of circular RNAs: No tautology
Dates: 17 November 2019 – 22 November 2019
Location: DE–Heidelberg

https://www.embl.de/training/events/2019/CIR19-01/index.html

 

Posted in Conference, General


Advanced Training with Oxford Nanopore Technologies

Posted on October 17, 2018 by

Join us for an advanced training experience using the Oxford Nanopore Technologies (ONT) platform. We will start with an introduction into ONT technology and devices, with the goal of covering end to end workflows for the preparation and analysis of human and yeast samples using whole genome and barcoded cDNA sequencing approaches. This course will cover the wet lab preparation of libraries from genomic DNA and total RNA, with a focus on the critical steps and potential pitfalls and understanding what constitutes a ‘good’ sample for purpose of best results using the technology. The training includes an overview of the MinKNOW GUI for GridION and MinION devices. We then cover methods available for basecalling and analysis of samples for structural variants and differential gene expression, using both Oxford Nanopore and open source tools.

More information and application at https://www.embl.de/training/events/2019/NAN19-01/index.html

Posted in Conference


Guardians of the transcriptome

Posted on October 11, 2018 by

Our new article on “Exon junction complexes suppress spurious splice sites to safeguard transcriptome integrity” is in press and will appear in Molecular Cell beginning of November. Congratulations to the team of authors: 

Volker Boehm1, Thiago Britto-Borges2,3, Anna-Lena Steckelberg1,4, Kusum K. Singh1,5, Jennifer V. Gerbracht1, Elif Gueney1, Lorea Blazquez6,7, Janine Altmüller8,9,10, Christoph Dieterich2,3, Niels H. Gehring1,11

Productive splicing of human pre-mRNAs requires the correct selection of authentic splice sites (SS) from the large pool of potential SS. Although SS consensus sequence and splicing regulatory proteins are known to influence SS usage, the mechanisms ensuring the effective suppression of cryptic SS are insufficiently explored. Here, we find that many aberrant exonic SS are efficiently silenced by the exon junction complex (EJC), a multi-protein complex that is deposited on spliced mRNA near the exon-exon junction. Upon depletion of EJC proteins, cryptic SS are de-repressed, leading to the mis-splicing of a broad set of mRNAs. Mechanistically, the EJC-mediated recruitment of the splicing regulator RNPS1 inhibits cryptic 5′SS usage, while the deposition of the EJC core directly masks reconstituted 3′SS, thereby precluding transcript disintegration. Thus, the EJC protects the transcriptome of mammalian cells from inadvertent loss of exonic sequences and safeguards the expression of intact, full length mRNAs.

Posted in General, Publications


DZHK PostDoc Start-up Grants awarded

Posted on March 1, 2018 by

Congratulations 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”

Posted in General


Our book on circular RNAs is out (Springer Press)

Posted on January 15, 2018 by

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




pulseR: Vielseitige computergestützte Analyse des RNA-Umsatzes aus metabolischen Markierungsexperimenten

Ein Paper, das unser neues Werkzeug zur Analyse von RNA-Sequenzen zur Markierung von RNA-Sequenzen beschreibt, ist jetzt online verfügbar!


Flexbar 3.0 - SIMD- und Multicore-Parallelisierung

Motivation:
Sequenziermaschinen mit hohem Durchsatz können viele Proben in einem einzigen Durchlauf verarbeiten. Für Illumina-Systeme werden Sequenz-Lesevorgänge mit einem zusätzlichen DNA-Tag versehen, das in den jeweiligen Sequenzierungsadaptern enthalten ist. Die Erkennung von Strichcode- und Adaptorsequenzen wird daher üblicherweise für die Analyse von Sequenzierungsdaten der nächsten Generation benötigt. Flexbar führt das Demultiplexen basierend auf Barcodes und Adapterabgleich für solche Daten durch. Weiterlesen...


Ein microRNA-129-5p / Rbfox-Crosstalk koordiniert das homöostatische Downscaling von exzitatorischen Synapsen - Neues Paper

Abstract: Synaptisches Downscaling ist ein homöostatischer Mechanismus, der es Neuronen erlaubt, die Feuerrate bei chronisch erhöhten Netzwerkaktivitäten zu reduzieren. Synaptisches Downscaling ist zwar wichtig für die Entwicklung von neuronalen Schaltkreisen und Epilepsie, die zugrundeliegenden Mechanismen sind jedoch kaum beschrieben. Wir führten kleine RNA-Profiling in Picrotoxin (PTX) behandelten Hippocampus-Neuronen, ein Modell der synaptischen Downscaling. Dabei identifizierten wir acht microRNAs (miRNAs), die als Reaktion auf PTX erhöht wurden, einschließlich miR-129-5p, deren Hemmung die synaptische Herabstufung in vitro blockierte und die Schwere der epileptischen Anfälle in vivo verringerte. Unter Verwendung von Transkriptom-, Proteom- und bioinformatischer Analyse identifizierten wir Calcium-Pumpe Atp2b4 und Doublecortin (Dcx) als miR-129-5p Ziele. Die Wiederherstellung der Atp2b4- und Dcx-Expression war ausreichend, um ein synaptisches Herunterskalieren in PTX-behandelten Neuronen zu verhindern. Darüber hinaus charakterisierten wir ein funktionelles Crosstalk zwischen miR-129-5p und dem RNA-bindenden Protein (RBP) Rbfox1. In Abwesenheit von PTX förderte Rbfox1 die Expression von Atp2b4 und Dcx. Bei der PTX-Behandlung wurde die Expression von Rbfox1 durch miR-129-5p herunterreguliert, wodurch Atp2b4 und Dcx unterdrückt werden konnten. Wir identifizierten daher ein neuartiges aktivitätsabhängiges miRNA / RBP-Crosstalk während der synaptischen Skalierung mit möglichen Implikationen für die Homöostase und Epileptogenese des Neuronalen Netzes.

Finden Sie mich auf Pubmed: www.ncbi.nlm.nih.gov/pubmed/28487411


Great Gordon Research Konferenz über RNA editing

Eine Woche wunderbare RNA modification Wissenschaft in Ventura / Kalifornien.


Rp-bp ist publiziert in NAR

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


Neue Publikation erschienen

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


JACUSA wurde publiziert

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

2 neue Publikationen

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

Unser Team hat sich weiter vergrößert

Wir begrüßen Ralf Hauenschild und Parisa Rezaee Borj in unserem Team!

Neue Publikation

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

Unser Team wird größer

Wir heißen Amit Singh und Aleksei Uvarovskii in unserem Team willkommen.

Talk bei der GCB 2016 in Berlin

Our software contribution

FUCHS – Towards full circular RNA characterization using RNAseq

has been selected for a talk at GCB2016

Neue Publikation

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.

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

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

Eine Zusammenarbeit mit unseren lieben Kollegen vom MPI-AGE wurde für die Publikation in Nature Communications akzeptiert.

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