Phosphorylation regulates the activity of the SMN complex during assembly of spliceosomal U snRNPs.
The assembly of spliceosomal U-rich small nuclear ribonucleoproteins (U snRNPs) is an ATP-dependent process mediated by the coordinated action of the SMN and the PRMT5 complex. Here, we provide evidence that the activity of this assembly machinery is regulated by means of post-translational modification. We show that two main components of the SMN/PRMT5 system, namely the survival motor neuron (SMN) protein (reduced levels thereof causing spinal muscular atrophy) and pICln, are phosphorylated in vivo. Both proteins share a previously unknown motif containing either one or two phosphoserines. Alteration of these residues in SMN (serines 28 and 31) significantly impairs the activity of the SMN complex. Despite the presence of SMN in both the nucleus and cytoplasm, we find that only the latter promotes efficient SMN-mediated U snRNP assembly activity. As cytoplasmic SMN is phosphorylated to a much larger extent, we hypothesize that this modification is a key activator of the SMN complex.
Grimmler
Matthias
M
Institute of Biochemistry, Biocenter at the University of Würzburg, Am Hubland, 97074 Würzburg, Germany.
Bauer
Liane
L
Nousiainen
Marjaana
M
Körner
Roman
R
Meister
Gunter
G
Fischer
Utz
U
D000595:Amino Acid Sequence; D017362:Cyclic AMP Response Element-Binding Protein / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D006367:HeLa Cells; D006801:Humans; D008969:Molecular Sequence Data; D046912:Multiprotein Complexes / Q000737:chemistry / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D010766:Phosphorylation; D011485:Protein Binding; D011496:Protein Methyltransferases / Q000378:metabolism; D011484:Protein-Arginine N-Methyltransferases; D016601:RNA-Binding Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D017411:Ribonucleoproteins, Small Nuclear / Q000378:metabolism*; D055532:SMN Complex Proteins; D016415:Sequence Alignment; D017381:Spliceosomes / Q000378:metabolism*; D014529:Uridine / Q000378:metabolism*
D017362:Cyclic AMP Response Element-Binding Protein; D046912:Multiprotein Complexes; D009419:Nerve Tissue Proteins; D016601:RNA-Binding Proteins; D017411:Ribonucleoproteins, Small Nuclear; D055532:SMN Complex Proteins; D011496:Protein Methyltransferases; C400529:PRMT5 protein, human; D011484:Protein-Arginine N-Methyltransferases; D014529:Uridine