Prof. Dr. Fischer
Colaboration with Prof. Dr. Jörg Vogel
PROJECT 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.
KEY TECHNOLOGIES :
- Classical RNP biochemistry
- X-ray crystallography
Reconstitution of the human U snRNP assembly machinery reveals stepwise Sm protein organization
Neuenkrichen, N., Englbrecht, C., Ohmer, J., Ziegenhals, T., Chari, A., and Fischer, U.
EMBO Journal 34(14):1925-41 (2015)
Stoll G, Pietiläinen OP, Linder B, Suvisaari J, Brosi C, Hennah W, Leppä V, Torniainen M, Ripatti S, Ala-Mello S, Plöttner O, Rehnström K, Tuulio-Henriksson A, Varilo T, Tallila J, Kristiansson K, Isohanni M, Kaprio J, Eriksson JG, Raitakari OT, Lehtimäki T, Jarvelin MR, Salomaa V, Hurles M, Stefansson H, Peltonen L, Sullivan PF, Paunio T, Lönnqvist J, Daly MJ, Fischer U*, Freimer NB*, Palotie A. 2013. *Corresponding authors.
Deletion of TOP3β, a component of FMRP-containing mRNPs, contributes to neurodevelopmental disorders. Nat. Neurosci. 16: 1228-1237
Highlighted in a News and Views article by Nott and Tsai in Nat. Neurosci. 16:1163-1164
Structural Basis of Assembly Chaperone- Mediated snRNP Formation
Grimm C, Chari A, Pelz JP, Kuper J, Kisker C, Diederichs K, Stark H, Schindelin H, Fischer U
Molecular Cell 49(4):692-703 (2013)
Intronic miR-26b controls neuronal differentiation by repressing its host transcript, ctdsp2
Dill H, Linder B, Fehr A, Fischer U
Genes & Development 26(1):25-30 (2012)
An assembly chaperone collaborates with the SMN complex to generate spliceosomal SnRNPs
Chari A, Golas M, Neuenkirchen N, Klingenhäger M, Sander B, Englbrecht C, Sickmann A, Stark H, Fischer U
Cell 135:497-509 (2008)