A specific subset of SR proteins shuttles continuously between the nucleus and the cytoplasm
A specific subset of SR proteins shuttles continuously between the nucleus and the cytoplasm
复制标题
DOI：
10.1101/gad.12.1.55
复制
发表时间：
1998-01-01
影响因子：
10.5
通讯作者：
Krainer, AR
中科院分区：
文献类型：
--
作者：
Cáceres, JF;Screaton, GR;Krainer, AR
SR蛋白构成组成性前mRNA剪接所需的核磷蛋白的大家族。这些因子对选择性剪接调节也具有全局的浓度依赖性作用，并且该活性被hnRNP A/B蛋白家族的成员拮抗。我们在这里表明，而一些人类SR蛋白局限于细胞核，其中三个-SF 2/ASF，SRp 20和9 G8-穿梭迅速，连续的细胞核和细胞质之间。通过交换穿梭和nonshuttling SR蛋白之间的相应结构域，我们表明，羧基末端精氨酸/丝氨酸丰富（RS）域是必需的穿梭。然而，该结构域不足以促进不相关的蛋白质报告基因的穿梭，这表明穿梭可能需要由RNA识别基序介导的稳定的RNA结合。与这种要求一致，SF 2/ASF的RRM 1中的双点突变损害RNA结合，从而阻止蛋白质穿梭。此外，我们发现RS结构域的磷酸化影响SR蛋白的穿梭特性。这些研究结果表明，不同的SR蛋白具有独特的细胞内转运特性，并表明穿梭的家族成员不仅在核前mRNA剪接中发挥作用，而且在mRNA转运、细胞质事件和/或涉及细胞核与细胞质之间通讯的过程中发挥作用。
The SR proteins constitute a large family of nuclear phosphoproteins required for constitutive pre-mRNA splicing. These factors also have global, concentration-dependent effects on alternative splicing regulation and this activity is antagonized by members of the hnRNP A/B family of proteins. We show here that whereas some human SR proteins are confined to the nucleus, three of them-SF2/ASF, SRp20, and 9G8-shuttle rapidly and continuously between the nucleus and the cytoplasm. By swapping the corresponding domains between shuttling and nonshuttling SR proteins, we show that the carboxy-terminal arginine/serine-rich (RS) domain is required for shuttling. This domain, however, is not sufficient to promote shuttling of an unrelated protein reporter, suggesting that stable RNA binding mediated by the RNA-recognition motifs may be required for shuttling. Consistent with such a requirement, a double point-mutation in RRM1 of SF2/ASF that impairs RNA binding prevents the protein from shuttling. In addition, we show that phosphorylation of the RS domain affects the shuttling properties of SR proteins. These findings show that different SR proteins have unique intracellular transport properties and suggest that the family members that shuttle may have roles not only in nuclear pre-mRNA splicing but also in mRNA transport, cytoplasmic events, and/or processes that involve communication between the nucleus and the cytoplasm.