M. Sendtner & M. Briese

The role of the non-coding RNAs Malat1 and 7SK in motoneuron physiology and motoneuron disease



Michael Sendtner Professor

Institut für Klinische Neurobiologie, Universität

Versbacherstr. 5, D-97078 Würzburg, Germany

Phone : 0931 201 44000
Fax : 0931 201 44009

E-Mail : Sendtner_M@ukw.de

Web : See online here



M. Briese

Institut für Klinische Neurobiologie

Versbacherstr. 5 97078 Würzburg

Phone : 0931-201-44008
Fax :

E-Mail : Briese_M@ukw.de

Web : No website available.

Motoneuron diseases such as amyotrophic lateral sclerosis (ALS) and spinal muscular atrophy (SMA) are characterized by loss of ubiquitously expressed proteins, yet manifest themselves as dysfunctions of motoneurons in particular. Since the disease-determining proteins such as TDP-43 and SMN are involved in RNA metabolism global alterations in RNA abundance and processing have been a major focus of investigations. However, it is becoming increasingly clear that specific defects in motor axons and at neuromuscular junctions are an early pathological hallmark of motoneuron diseases. In this context we are investigating how transcriptome alterations in axons of dysfunctional motoneurons might contribute to such pre-synaptic defects and whether changes in non-coding transcripts might play a part in such alterations. In our project we plan to investigate the role of the non-coding RNAs Malat1 and 7SK in motoneuron diseases with particular emphasis on their roles in regulating axonal transcript levels. For this purpose we are using compartmentalized motoneuron cultures in combination with high-throughput sequencing techniques to investigate putative changes in the RNA contents of motor axons. Furthermore, we are applying techniques such as iCLIP to investigate how transcriptome changes in motoneuron diseases are guided by RNA-binding proteins. Finally, we are studying mouse models of motoneuron diseases to evaluate the role of these noncoding RNAs in the underlying pathomechanism. Overall, the aim of our research is to investigate local transcriptome disturbances in diseased motor axons and probe the contribution of noncoding RNAs to such defects.

Key technologies:
- iCLIP
- compartmentalized motoneuron cultures

Google Scholars :

http://scholar.google.com/citations?user=5Fej5hIAAAAJ&hl=en

Last Publications

Briese M, Saal L, Appenzeller S, Moradi M, Baluapuri A, Sendtner M. 2015. Whole transcriptome profiling reveals the RNA content of motor axons. Nucl. Acids Res. doi: 10.1093/nar/gkv1027

Saal L, Briese M, Kneitz S, Glinka M, Sendtner M. 2014. Subcellular transcriptome alterations in a cell culture model of spinal muscular atrophy point to widespread defects in axonal growth and presynaptic differentiation. RNA 20: 1789-1802.

Wagnon JL, Briese M, Sun W, Mahaffey CL, Curk T, Rot G, Ule J, Frankel WN. 2012. CELF4 regulates translation and local abundance of a vast set of mRNAs, including genes associated with regulation of synaptic function. PLoS Genet 8: e1003067.

Tollervey JR, Curk T, Rogelj B, Briese M, Cereda M, Kayikci M, Konig J, Hortobagyi T, Nishimura AL, Zupunski V, et al. 2011. Characterizing the RNA targets and position-dependent splicing regulation by TDP-43. Nat Neurosci 14: 452-458.

Wiese S, Herrmann T, Drepper C, Jablonka S, Funk N, Klausmeyer A, Rogers ML, Rush R, Sendtner M. 2010. Isolation and enrichment of embryonic mouse motoneurons from the lumbar spinal cord of individual mouse embryos. Nat Protoc 5: 31-38.

Glinka M, Herrmann T, Funk N, Havlicek S, Rossoll W, Winkler C, Sendtner M. 2010. The heterogeneous nuclear ribonucleoprotein-R is necessary for axonal beta-actin mRNA translocation in spinal motor neurons. Hum Mol Genet 19: 1951-1966.