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

Nucleic Acids Res. 2021 Jun 21;49(11):6437-6455. doi: 10.1093/nar/gkab452.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Autophagy-Related Protein-1 Homolog / antagonists & inhibitors
  • Autophagy-Related Protein-1 Homolog / metabolism*
  • Autophagy-Related Protein-1 Homolog / physiology
  • Cell Line
  • Coiled Bodies
  • Humans
  • Intracellular Signaling Peptides and Proteins / antagonists & inhibitors
  • Intracellular Signaling Peptides and Proteins / metabolism*
  • Intracellular Signaling Peptides and Proteins / physiology
  • Ion Channels / metabolism
  • Phosphorylation
  • Protein-Arginine N-Methyltransferases / metabolism
  • Ribonucleoproteins, Small Nuclear / biosynthesis*

Substances

  • Intracellular Signaling Peptides and Proteins
  • Ion Channels
  • Ribonucleoproteins, Small Nuclear
  • PRMT5 protein, human
  • Protein-Arginine N-Methyltransferases
  • Autophagy-Related Protein-1 Homolog
  • ULK1 protein, human