Specific sequences of the Sm and Sm-like (Lsm) proteins mediate their interaction with the spinal muscular atrophy disease gene product (SMN).
The spinal muscular atrophy disease gene product (SMN) is crucial for small nuclear ribonuclear protein (snRNP) biogenesis in the cytoplasm and plays a role in pre-mRNA splicing in the nucleus. SMN oligomers interact avidly with the snRNP core proteins SmB, -D1, and -D3. We have delineated the specific sequences in the Sm proteins that mediate their interaction with SMN. We show that unique carboxyl-terminal arginine- and glycine-rich domains comprising the last 29 amino acids of SmD1 and the last 32 amino acids of SmD3 are necessary and sufficient for SMN binding. Interestingly, SMN also interacts with at least two of the U6-associated Sm-like (Lsm) proteins, Lsm4 and Lsm6. Furthermore, the carboxyl-terminal arginine- and glycine-rich domain of Lsm4 directly interacts with SMN. This suggests that SMN also functions in the assembly of the U6 snRNP in the nucleus and in the assembly of other Lsm-containing complexes. These findings demonstrate that arginine- and glycine-rich domains are necessary and sufficient for SMN interaction, and they expand further the range of targets of the SMN protein.
Friesen
W J
WJ
Howard Hughes Medical Institute and Department of Biochemistry & Biophysics, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104-6148, USA.
Dreyfuss
G
G
D000595:Amino Acid Sequence; D001120:Arginine / Q000378:metabolism; D001324:Autoantigens / Q000378:metabolism; D017362:Cyclic AMP Response Element-Binding Protein; D005998:Glycine / Q000378:metabolism; D006801:Humans; D008969:Molecular Sequence Data; D009134:Muscular Atrophy, Spinal; D009419:Nerve Tissue Proteins / Q000737:chemistry* / Q000378:metabolism*; D011485:Protein Binding; D016601:RNA-Binding Proteins; D017411:Ribonucleoproteins, Small Nuclear / Q000737:chemistry* / Q000378:metabolism*; D055532:SMN Complex Proteins; D013329:Structure-Activity Relationship; D055517:snRNP Core Proteins
D001324:Autoantigens; D017362:Cyclic AMP Response Element-Binding Protein; C485751:LSM4 protein, human; D009419:Nerve Tissue Proteins; D016601:RNA-Binding Proteins; D017411:Ribonucleoproteins, Small Nuclear; D055532:SMN Complex Proteins; C526407:SNRPB protein, human; C526409:SNRPD1 protein, human; C526412:SNRPD3 protein, human; C526417:SNRPN protein, human; C526416:Snrpb protein, mouse; C489793:Snrpd1 protein, mouse; D055517:snRNP Core Proteins; D001120:Arginine; D005998:Glycine