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SPP1935 -- Deciphering the mRNP code :
RNA-bound Determinants of Post-transcriptional Gene Regulation

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laboratoriesProf. Dr. Vogel

Jörg Vogel Center
Institute of Molecular Infection Biology, University of Würzburg

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Josef-Schneider-Str. 2/D15 D-97080 Würzburg

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+49-931-3182576


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Post-transcriptional control of TOP mRNAs in response to nutritional signals

Colaboration with Prof. Dr. Utz Fischer



Lab InfoPROJECT INFORMATION :

The control of translation is facilitated in many cases by trans acting factors that interact with the transcript in a regulated and dynamic manner. An interesting group of transcripts that show tight regulation in response to mitogenic and nutritional signals are mRNAs encoding for components of the mammalian protein synthesis machinery (ribosomal proteins and elongation factors). A unique sequence element, termed the 5' Terminal OligoPyrimidine tract (5'-TOP) characterizes this group of mRNAs. This motif comprises the core of a translational regulatory element in cis. The post transcriptional control of these TOP mRNAs manifests by their selective and reversible shift from polysomes in dividing cells into subpolysomal mRNP particles in quiescent or starving cells. Several factors have been implicated in TOP mRNA regulation but it is still unclear how this is achieved at the mechanistic level and whether the TOP mRNP composition as a whole changes in response to nutritional conditions. We have established a new technique termed Grad-seq that allows the systematic and comprehensive investigation of mRNP composition in cellular extracts. Using this technique along with traditional biochemical approaches we will investigate the biochemical composition of TOP mRNAs under normal conditions and upon starvation strategies. The identification of factors that selectively bind to TOP mRNAs under defined conditions will help to understand how the biosynthesis of the translational machinery is accomplished at the post-transcriptional level.



Lab techsKEY TECHNOLOGIES :

RNA-seq,
Grad-seq,
CLIP,
single-cell RNA-seq



PublicationsPUBLICATIONS :

Westermann AJ, Förstner KU, Amman F, Barquist L, Chao Y, Schulte LN, Müller L, Reinhardt R, Stadler PF, Vogel J (2016)
Dual RNA-seq unveils noncoding RNA functions in host-pathogen interactions
Nature 529:496-501

Smirnov A, Förstner KU, Holmqvist E, Otto A, Günster R, Becher D, Reinhardt R, Vogel J (2016)
Grad-seq guides the discovery of ProQ as a major small RNA binding protein
PNAS in press

Papenfort K, Sun Y, Miyakoshi M, Vanderpool CK, Vogel J (2013)
Small RNA-mediated activation of sugar phosphatase mRNA regulates glucose homeostasis
Cell 153:426–437

Deltcheva E, Chylinski K, Sharma CM, Gonzales K, Chao Y, Pirzada ZA, Eckert MR, Vogel J, Charpentier E (2011)
CRISPR RNA maturation by trans-encoded small RNA and host factor RNase III
Nature 471(7340):602-7

Sharma CM, Hoffmann S, Darfeuille F, Reignier J, Findeiß S, Sittka A, Chabas S, Reiche K, Hackermüller J,
Reinhardt R, Stadler PF, Vogel J (2010)
The primary transcriptome of the major human pathogen Helicobacter pylori
Nature 464(7285)250-255