Differential effects of hyperphosphorylation on splicing factor SRp55
Differential effects of hyperphosphorylation on splicing factor SRp55
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DOI：
10.1042/bj20021827
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发表时间：
2003-05-01
影响因子：
4.1
通讯作者：
Tarn, WY
中科院分区：
文献类型：
--
作者：
Lai, MC;Lin, RI;Tarn, WY
富含丝氨酸/精氨酸 (SR) 蛋白家族的成员在前体 mRNA 的组成型剪接和调节剪接中发挥着重要作用。富含精氨酸/丝氨酸二肽的结构域（RS 结构域）的磷酸化可以调节 SR 蛋白的活性和亚细胞定位。然而，SR蛋白家族成员是否受到单独调控以及如何实现这一点仍不清楚。在本报告中，我们表明 5,6-二氯-1β-D-呋喃核糖基-苯并咪唑 (DRB) 是一种 RNA 聚合酶 II 依赖性转录抑制剂，可特异性诱导 SRp55 的过度磷酸化，但不会诱导任何其他测试的 SR 蛋白的过度磷酸化。 SRp55 的过度磷酸化发生在 RS 结构域，并且似乎需要 RNA 结合活性。 DRB 处理后，过度磷酸化的 SRp55 重新定位到扩大的核斑点。有趣的是，当 SR 蛋白激酶 Clk/Sty 过度表达时，SRp55 专门被蛋白酶体降解。尽管不稳定信号位于 SRp55 C 端 43 个氨基酸片段内，但其相邻的富含赖氨酸/丝氨酸的 RS 结构域对于 Clk/Sty 介导的降解仍然至关重要。我们首次报道SRp55在不同情况下可以过度磷酸化，从而其命运受到不同的影响。
Members of the serine/arginine-rich (SR) protein family play an important role in both constitutive and regulated splicing of precursor mRNAs. Phosphorylation of the arginine/serine dipeptide-rich domain (RS domain) can modulate the activity and the subcellular localization of SR proteins. However, whether the SR protein family members are individually regulated and how this is achieved remain unclear. In this report we show that 5,6-dichloro-1beta-D-ribofuranosyl-benzimidazole (DRB), an inhibitor of RNA polymerase II-dependent transcription, specifically induced hyperphosphorylation of SRp55 but not that of any other SR proteins tested. Hyperphosphorylation of SRp55 occurs at the RS domain and appears to require the RNA-binding activity. Upon DRB treatment, hyperphosphorylated SRp55 relocates to enlarged nuclear speckles. Intriguingly, SRp55 is specifically targeted for degradation by the proteasome upon overexpression of the SR protein kinase Clk/Sty. Although a destabilization signal is mapped within the C-terminal 43-amino acid segment of SRp55, its adjacent lysine/serine-rich RS domain is nevertheless critical for the Clk/Sty-mediated degradation. We report for the first time that SRp55 can be hyperphosphorylated under different circumstances whereby its fate is differentially influenced.