Regulation of adenovirus alternative RNA splicing by dephosphorylation of SR proteins
Regulation of adenovirus alternative RNA splicing by dephosphorylation of SR proteins
复制标题
DOI：
10.1038/30277
复制
发表时间：
1998-05-14
期刊：
影响因子：
64.8
通讯作者：
Akusjärvi, G
中科院分区：
文献类型：
--
作者：
Kanopka, A;Mühlemann, O;Akusjärvi, G
SR蛋白是剪接体组装过程中剪接位点早期识别所需的基本剪接因子家族（1，2）。当在体内过表达或在体外过量添加到提取物中时，它们也作为替代RNA剪接因子发挥作用（1，2）。SR蛋白在体内高度磷酸化，这是其在剪接体组装（3，4）和剪接催化（5，6）中的功能所需的修饰。在这里，我们表明，从晚期腺病毒感染的细胞中纯化的SR蛋白被灭活为剪接增强子或剪接阻遏蛋白由病毒诱导的去磷酸化。我们进一步表明，病毒编码的蛋白E4-ORF 4激活去磷酸化的HeLa SR蛋白的蛋白磷酸酶2A，并将其剪接特性转化为从晚期腺病毒感染的细胞纯化的SR蛋白。综上所述，我们的研究结果表明，E4-ORF 4是一个重要的因素控制的时间转移腺病毒的选择性RNA剪接，我们的结论是，选择性前mRNA剪接，像许多其他的生物过程，是由可逆的蛋白磷酸化。
SR proteins are a family of essential splicing factors required for early recognition of splice sites during spliceosome assembly(1,2). They also function as alternative RNA splicing factors when overexpressed in vivo or added in excess to extracts in vitro(1,2). SR proteins are highly phosphorylated in vivo, a modification that is required for their function in spliceosome assembly(3,4) and splicing catalysis(5,6). Here we show that SR proteins purified from late adenovirus-infected cells are inactivated as splicing enhancer or splicing repressor proteins by virus-induced dephosphorylation. We further show that the virus-encoded protein E4-ORF4 activates dephosphorylation by protein phosphatase 2A of HeLa SR proteins and converts their splicing properties into that of SR proteins purified from late adenovirus-infected cells. Taken together, our results suggest that E4-ORF4 is an important factor controlling the temporal shift in adenovirus alternative RNA splicing,We conclude that alternative pre-mRNA splicing, like many other biological processes, is regulated by reversible protein phosphorylation.