An essential role of the autophagy activating kinase ULK1 in snRNP biogenesis

Author:

Schmitz Katharina1,Cox Jan1,Esser Lea Marie1,Voss Martin12,Sander Katja1,Löffler Antje1,Hillebrand Frank3,Erkelenz Steffen34ORCID,Schaal Heiner3ORCID,Kähne Thilo5,Klinker Stefan6,Zhang Tao67,Nagel-Steger Luitgard67,Willbold Dieter67,Seggewiß Sabine1,Schlütermann David1,Stork Björn1,Grimmler Matthias89,Wesselborg Sebastian1,Peter Christoph1ORCID

Affiliation:

1. Institute of Molecular Medicine I, Medical Faculty, Heinrich Heine University Düsseldorf, Düsseldorf, Germany

2. Institute of Biochemistry, University of Cologne, Cologne, Germany

3. Institute of Virology, University Hospital Düsseldorf, Düsseldorf, Germany

4. Institute for Genetics and Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD), University of Cologne, Cologne, Germany

5. Insitute of Experimental Internal Medicine, Otto von Guericke University, Magdeburg, Germany

6. Institut für Physikalische Biologie, Heinrich-Heine-Universität Düsseldorf, Germany

7. Institute of Biological Information Processing (Structural Biochemistry: IBI-7), Forschungszentrum Jülich, Jülich, Germany

8. Hochschule Fresenius, Idstein, Germany

9. DiaSys Diagnostic Systems GmbH, Alte Strasse 9, 65558 Holzheim, Germany

Abstract

Abstract The biogenesis of small uridine-rich nuclear ribonucleoproteins (UsnRNPs) depends on the methylation of Sm proteins catalyzed by the methylosome and the subsequent action of the SMN complex, which assembles the heptameric Sm protein ring onto small nuclear RNAs (snRNAs). In this sophisticated process, the methylosome subunit pICln (chloride conductance regulatory protein) is attributed to an exceptional key position as an ‘assembly chaperone’ by building up a stable precursor Sm protein ring structure. Here, we show that—apart from its autophagic role—the Ser/Thr kinase ULK1 (Uncoordinated [unc-51] Like Kinase 1) functions as a novel key regulator in UsnRNP biogenesis by phosphorylation of the C-terminus of pICln. As a consequence, phosphorylated pICln is no longer capable to hold up the precursor Sm ring structure. Consequently, inhibition of ULK1 results in a reduction of efficient UsnRNP core assembly. Thus ULK1, depending on its complex formation, exerts different functions in autophagy or snRNP biosynthesis.

Funder

Deutsche Forschungsgemeinschaft

DFG

Helmholtz-Validierungsfonds of the Impuls and Vernetzungs-Fonds der Helmholtzgemeinschaft

University of Düsseldorf

Publisher

Oxford University Press (OUP)

Subject

Genetics

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