Michael Briese

Institute of Clinical Neurobiology
University Hospital Wuerzburg

E-mail: Briese_M(at)ukw.de

Michael Sendtner

Institute of Clinical Neurobiology
University Hospital Wuerzburg

E-mail: Sendtner_M(at)ukw.de

For more information and contact visit the institut's website.

Abstract

Spinal motoneurons are highly polarized cells that critically depend on subcellular mRNA transport into axons during development, and for maintenance and repair in the adult. Axonal mRNA transport is disturbed in motoneuron diseases such as spinal muscular atrophy (SMA) and amyotrophic lateral sclerosis (ALS), which might contribute to defective axon integrity and synaptic transmission at neuromuscular endplates, thereby causing motoneuron dysfunction and death.

Recent research found disturbed assembly and transport of messenger ribonucleoprotein particles (mRNPs) in motoneuron disorders. We have previously identified the heterogeneous nuclear ribonucleoprotein R (hnRNP R), an RNA-binding protein, as an interactor of proteins involved in SMA and ALS. Reduction of hnRNP R in cultured primary mouse motoneurons leads to reduced axon growth indicating that it has important roles in motoneuron development. In axons of motoneurons, hnRNP R is a component of transport mRNPs and regulates the local translation of many proteins involved in axon growth and synaptic integrity.

Our project is designed to characterize the hnRNP R transport mRNPs and investigate to what extent their integrity is disturbed in mouse models of motoneuron diseases. Additionally, we are planning to investigate the functions of hnRNP R for motor system development and maintenance in vivo.

Project-related publications

Ji C, Bader J, Ramanathan P, Hennlein L, Meissner F, Jablonka S, Mann M, Fischer U, Sendtner M, Briese M. Interaction of 7SK with the Smn complex modulates snRNP production. Nat Commun. 2021 Feb 24;12(1):1278. doi: 10.1038/s41467-021-21529-1.

Briese M, Saal-Bauernschubert L, Ji C, Moradi M, Ghanawi H, Uhl M, Appenzeller S, Backofen R, Sendtner M. hnRNP R and its main interactor, the noncoding RNA 7SK, coregulate the axonal transcriptome of motoneurons. Proc Natl Acad Sci U S A. 2018 Mar 20;115(12):E2859-E2868. doi: 10.1073/pnas.1721670115.