Specific sequences of the Sm and Sm-like (Lsm) proteins mediate their interaction with the spinal muscular atrophy disease gene product (SMN)
Specific sequences of the Sm and Sm-like (Lsm) proteins mediate their interaction with the spinal muscular atrophy disease gene product (SMN)
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DOI：
10.1074/jbc.m003299200
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发表时间：
2000-08-25
影响因子：
4.8
通讯作者：
Dreyfuss, G
中科院分区：
文献类型：
--
作者：
Friesen, MJ;Dreyfuss, G
脊髓性肌萎缩症基因产物 (SMN) 对于细胞质中小核核糖核蛋白 (snRNP) 的生物合成至关重要，并在细胞核中的前 mRNA 剪接中发挥作用。 SMN 寡聚物与 snRNP 核心蛋白 SmB、-D1 和 -D3 强烈相互作用。我们已经描述了 Sm 蛋白中介导其与 SMN 相互作用的特定序列。我们证明，包含 SmD1 的最后 29 个氨基酸和 SmD3 的最后 32 个氨基酸的独特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 U6 相关 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 还在细胞核中 U6 snRNP 的组装以及其他含有 Lsm 的复合物的组装中发挥作用。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，并且它们进一步扩展了 SMN 蛋白的靶标范围。
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.