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New Signaling Pathway in Neurons

02/25/2021

A new signaling pathway has been identified that can prevent the overproduction of certain RNA-protein complexes in neurons. These complexes play an important role in neurodegenerative diseases.

The molecule Larp7 plays an important role in the assembly of snRNP complexes. It accumulates in nerve cells (arrow) where the complexes are formed.
The molecule Larp7 plays an important role in the assembly of snRNP complexes. It accumulates in nerve cells (arrow) where the complexes are formed. (Image: Changhe Ji / Universität Würzburg)

Neurodegenerative diseases, such as various forms of senile dementia or amyotrophic lateral sclerosis (ALS), have one thing in common: large amounts of certain RNA-protein complexes (snRNPs) are produced and deposited in the nerve cells of those affected – and this hinders the function of the cells. The overproduction is possibly caused by a malfunction in the assembly of the protein complexes.

How the production of these protein complexes is regulated was unknown until now. Researchers from Martinsried and Würzburg in Bavaria, Germany, have solved the puzzle and now report on it in the open access journal Nature Communications. They describe in detail a signaling pathway that prevents the overproduction of snRNPs when they are not needed. The results should make it possible to better understand the processes in motor neuron diseases and senile dementia.

The research group led by Professor Michael Sendtner and Dr. Michael Briese from the Institute of Clinical Neurobiology at Julius-Maximilians-Universität Würzburg (JMU) was in charge of the publication. Professor Utz Fischer and Pradhipa Ramanathan from the JMU Institute of Biochemistry were also involved, as was a team from the Max Planck Institute of Biochemistry in Martinsried.

The next steps in research

Further investigations shall now show how the synthesis and degradation of excess snRNPs are regulated in nerve cells. The scientists hope that in the end they will be able to identify new therapeutic options for neurodegenerative diseases.

This work was financially supported by the German Research Foundation and the European Research Council.

Publication

Ji, C., Bader, J., Ramanathan, P. et al. Interaction of 7SK with the Smn complex modulates snRNP production. Nature Communications 12, 1278 (24 February 2021). https://doi.org/10.1038/s41467-021-21529-1

Contact person

Prof. Dr. Michael Sendtner, Institute for Clinical Neurobiology, University Hospital Würzburg, T +49 931 201-44000, sendtner_m@ukw.de

By Robert Emmerich

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