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CrackEpitranscriptom SIGNED

Cracking the epitranscriptome

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EC-Contrib. €

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Project "CrackEpitranscriptom" data sheet

The following table provides information about the project.

Coordinator
WEIZMANN INSTITUTE OF SCIENCE 

Organization address
address: HERZL STREET 234
city: REHOVOT
postcode: 7610001
website: www.weizmann.ac.il

contact info
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name: n.a.
surname: n.a.
function: n.a.
email: n.a.
telephone: n.a.
fax: n.a.

 Coordinator Country Israel [IL]
 Total cost 1˙402˙666 €
 EC max contribution 1˙402˙666 € (100%)
 Programme 1. H2020-EU.1.1. (EXCELLENT SCIENCE - European Research Council (ERC))
 Code Call ERC-2016-STG
 Funding Scheme ERC-STG
 Starting year 2016
 Duration (year-month-day) from 2016-11-01   to  2021-10-31

 Partnership

Take a look of project's partnership.

# participants  country  role  EC contrib. [€] 
1    WEIZMANN INSTITUTE OF SCIENCE IL (REHOVOT) coordinator 1˙402˙666.00

Map

 Project objective

Over 100 types of distinct modifications are catalyzed on RNA molecules post-transcriptionally. In an analogous manner to well-studied chemical modifications on proteins or DNA, modifications on RNA - and particularly on mRNA - harbor the exciting potential of regulating the complex and interlinked life cycle of these molecules. The most abundant modification in mammalian and yeast mRNA is N6-methyladenosine (m6A). We have pioneered approaches for mapping m6A in a transcriptome wide manner, and we and others have identified factors involved in encoding and decoding m6A. While experimental disruption of these factors is associated with severe phenotypes, the role of m6A remains enigmatic. No single methylated site has been shown to causally underlie any physiological or molecular function. This proposal aims to establish a framework for systematically deciphering the molecular function of a modification and its underlying mechanisms and to uncover the physiological role of the modification in regulation of a cellular response. We will apply this framework to m6A in the context of meiosis in budding yeast, as m6A dynamically accumulates on meiotic mRNAs and as the methyltransferase catalyzing m6A is essential for meiosis. We will (1) aim to elucidate the physiological targets of methylation governing entry into meiosis (2) seek to elucidate the function of m6A at the molecular level, and understand its impact on the various steps of the mRNA life cycle, (3) seek to understand the mechanisms underlying its effects. These aims will provide a comprehensive framework for understanding how the epitranscriptome, an emerging post-transcriptional layer of regulation, fine-tunes gene regulation and impacts cellular decision making in a dynamic response, and will set the stage towards dissecting the roles of m6A and of an expanding set of mRNA modifications in more complex and disease related systems.

 Publications

year authors and title journal last update
List of publications.
2017 Modi Safra, Ronit Nir, Daneyal Farouq, Ilya Vainberg Slutskin, Schraga Schwartz
TRUB1 is the predominant pseudouridine synthase acting on mammalian mRNA via a predictable and conserved code
published pages: 393-406, ISSN: 1088-9051, DOI: 10.1101/gr.207613.116
Genome Research 27/3 2019-06-13
2017 Modi Safra, Aldema Sas-Chen, Ronit Nir, Roni Winkler, Aharon Nachshon, Dan Bar-Yaacov, Matthias Erlacher, Walter Rossmanith, Noam Stern-Ginossar, Schraga Schwartz
The m1A landscape on cytosolic and mitochondrial mRNA at single-base resolution
published pages: , ISSN: 0028-0836, DOI: 10.1038/nature24456
Nature 2019-06-13
2019 Roni Winkler, Ella Gillis, Lior Lasman, Modi Safra, Shay Geula, Clara Soyris, Aharon Nachshon, Julie Tai-Schmiedel, Nehemya Friedman, Vu Thuy Khanh Le-Trilling, Mirko Trilling, Michal Mandelboim, Jacob H. Hanna, Schraga Schwartz, Noam Stern-Ginossar
m6A modification controls the innate immune response to infection by targeting type I interferons
published pages: 173-182, ISSN: 1529-2908, DOI: 10.1038/s41590-018-0275-z
Nature Immunology 20/2 2019-06-06
2018 Arjan P.M. de Brouwer, Rami Abou Jamra, Nadine Körtel, Clara Soyris, Daniel L. Polla, Modi Safra, Avia Zisso, Christopher A. Powell, Pedro Rebelo-Guiomar, Nadja Dinges, Violeta Morin, Michael Stock, Mureed Hussain, Mohsin Shahzad, Saima Riazuddin, Zubair M. Ahmed, Rolph Pfundt, Franziska Schwarz, Lonneke de Boer, André Reis, Detilina Grozeva, F. Lucy Raymond, Sheikh Riazuddin, David A. Koolen, Michal Minczuk, Jean-Yves Roignant, Hans van Bokhoven, Schraga Schwartz
Variants in PUS7 Cause Intellectual Disability with Speech Delay, Microcephaly, Short Stature, and Aggressive Behavior
published pages: 1045-1052, ISSN: 0002-9297, DOI: 10.1016/j.ajhg.2018.10.026
The American Journal of Human Genetics 103/6 2019-06-06

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