Toward an assembly line for U7 snRNPs: interactions of U7-specific Lsm proteins with PRMT5 and SMN complexes.
The survival of motor neurons (SMN) complex mediates the assembly of small nuclear ribonucleoproteins (snRNPs) involved in splicing and histone RNA processing. A crucial step in this process is the binding of Sm proteins onto the SMN protein. For Sm B/B', D1, and D3, efficient binding to SMN depends on symmetrical dimethyl arginine (sDMA) modifications of their RG-rich tails. This methylation is achieved by another entity, the PRMT5 complex. Its pICln subunit binds Sm proteins whereas the PRMT5 subunit catalyzes the methylation reaction. Here, we provide evidence that Lsm10 and Lsm11, which replace the Sm proteins D1 and D2 in the histone RNA processing U7 snRNPs, associate with pICln in vitro and in vivo without receiving sDMA modifications. This implies that the PRMT5 complex is involved in an early stage of U7 snRNP assembly and hence may have a second snRNP assembly function unrelated to sDMA modification. We also show that the binding of Lsm10 and Lsm11 to SMN is independent of any methylation activity. Furthermore, we present evidence for two separate binding sites in SMN for Sm/Lsm proteins. One recognizes Sm domains and the second one, the sDMA-modified RG-tails, which are present only in a subset of these proteins.
Azzouz
Teldja N
TN
Institute of Cell Biology, University of Bern, Baltzerstrasse 4, 3012 Bern, Switzerland.
Pillai
Ramesh S
RS
Däpp
Christoph
C
Chari
Ashwin
A
Meister
Gunter
G
Kambach
Christian
C
Fischer
Utz
U
Schümperli
Daniel
D
D001120:Arginine / Q000031:analogs & derivatives / Q000737:chemistry; D001665:Binding Sites; D002384:Catalysis; D002460:Cell Line; D003593:Cytoplasm / Q000378:metabolism; D019175:DNA Methylation; D005982:Glutathione Transferase / Q000378:metabolism; D006657:Histones / Q000737:chemistry / Q000378:metabolism; D006801:Humans; D047468:Immunoprecipitation; D066298:In Vitro Techniques; D007473:Ion Channels / Q000378:metabolism; D009046:Motor Neurons / Q000378:metabolism*; D010957:Plasmids / Q000378:metabolism; D011485:Protein Binding; D014176:Protein Biosynthesis; D011496:Protein Methyltransferases / Q000737:chemistry*; D017434:Protein Structure, Tertiary; D011484:Protein-Arginine N-Methyltransferases; D012313:RNA / Q000737:chemistry; D012326:RNA Splicing; D016601:RNA-Binding Proteins / Q000502:physiology; D020885:Ribonucleoprotein, U7 Small Nuclear / Q000737:chemistry* / Q000378:metabolism; D017411:Ribonucleoproteins, Small Nuclear / Q000502:physiology; D017381:Spliceosomes / Q000378:metabolism; D014158:Transcription, Genetic; D014162:Transfection; D020798:Two-Hybrid System Techniques
D001120:Arginine; D005982:Glutathione Transferase; D006657:Histones; D007473:Ion Channels; D011496:Protein Methyltransferases; D011484:Protein-Arginine N-Methyltransferases; D012313:RNA; D016601:RNA-Binding Proteins; D020885:Ribonucleoprotein, U7 Small Nuclear; D017411:Ribonucleoproteins, Small Nuclear; C410035:CLNS1A protein, human; C438196:LSM10 protein, human; C506080:LSM11 protein, human; C477938:Lsm11 protein, mouse; C487735:dimethylarginine; C400529:PRMT5 protein, human