Friesen W J, Dreyfuss G
Howard Hughes Medical Institute and Department of Biochemistry & Biophysics, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104-6148, USA.
J Biol Chem. 2000 Aug 25;275(34):26370-5. doi: 10.1074/jbc.M003299200.
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.
脊髓性肌萎缩症疾病基因产物（SMN）对于细胞质中核小核糖核蛋白（snRNP）的生物合成至关重要，并且在细胞核中的前体mRNA剪接过程中发挥作用。SMN寡聚体与snRNP核心蛋白SmB、-D1和-D3紧密相互作用。我们已经确定了Sm蛋白中介导其与SMN相互作用的特定序列。我们发现，由SmD1的最后29个氨基酸和SmD3的最后32个氨基酸组成的独特的羧基末端富含精氨酸和甘氨酸的结构域对于SMN结合是必要且充分的。有趣的是，SMN还与至少两种与U6相关的Sm样（Lsm）蛋白Lsm4和Lsm6相互作用。此外，Lsm4的羧基末端富含精氨酸和甘氨酸的结构域直接与SMN相互作用。这表明SMN在细胞核中U6 snRNP的组装以及其他含Lsm的复合物的组装中也发挥作用。这些发现表明，富含精氨酸和甘氨酸的结构域对于SMN相互作用是必要且充分的，并且它们进一步扩大了SMN蛋白的靶标范围。
