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 w ith the snRNP core proteins SmB, -D1, and -D3. We have delineated the speci fic sequences in the Sm proteins that mediate their interaction with SMN. W e show that unique carboxyl-terminal arginine- and glycine-rich domains com prising 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 inte racts with at least two of the U6-associated Sm-like (Lsm) proteins, Lsm4 a nd Lsm6. Furthermore, the carboxyl-terminal arginine- and glycine-rich doma in of Lsm4 directly interacts with SMN. This suggests that SMN also functio ns in the assembly of the U6 snRNP in the nucleus and in the assembly of ot her 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.