Negative feedback regulation among SR splicing factors encoded by Rbp1 and Rbp1-like in Drosophila
Negative feedback regulation among SR splicing factors encoded by Rbp1 and Rbp1-like in Drosophila
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DOI：
10.1038/sj.emboj.7600723
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发表时间：
2005-07-20
期刊：
影响因子：
11.4
通讯作者：
Lopez, AJ
中科院分区：
文献类型：
--
作者：
Kumar, S;Lopez, AJ
SR蛋白是一个广泛保守的剪接调控蛋白家族。SR蛋白的负性自我调节被认为是在剪接环境中实施动态平衡控制的，但研究的例子很少，缺乏RS结构域的异构体的作用也不清楚。我们发现编码哺乳动物SRp20的果蝇同源物的基因Rbp1和Rbp1-like在选择性剪接位点选择的水平上负向自我调节和交叉调节。这调节了富含丝氨酸和苏氨酸的RS结构域或无关的C末端结构域(ALT)的异构体的相对表达。RBP1-ALT对双性和类Rbp1剪接的影响与RBP1-RS和RBP1L-RS相反。RBP1-ALT和-RS对ALT/RS比值具有相反的负反馈作用。而RBP1-ALT抑制RBP1-RS的表达，而刺激RBP1L-RS的表达。这种不对称性可能有助于在发育过程中观察到RBP1-RS/RBP1L-RS比率的变化。这些结果提供了反馈调节的SR蛋白网络的第一个例子，证明了替代异构体具有活跃的动态平衡作用。
SR proteins constitute a widely conserved family of splicing regulators. Negative autoregulation of SR proteins has been proposed to exert homeostatic control on the splicing environment, but few examples have been studied and the role of isoforms that lack the RS domain is unclear. We show that genes Rbp1 and Rbp1-like, which encode Drosophila homologs of mammalian SRp20, negatively autoregulate and crossregulate at the level of alternative 30 splice site selection. This adjusts the relative expression of isoforms with either an RS domain or unrelated C-terminal domains (ALT) that are rich in serine and threonine. The effects of RBP1-ALT on splicing of doublesex and Rbp1-like are opposite to those of RBP1-RS and RBP1L-RS. RBP1-ALT and -RS exert opposing negative feedback on the ALT/RS ratio. However, RBP1-ALT inhibits the expression of RBP1-RS while stimulating that of RBP1L-RS. This asymmetry may contribute to changes in the RBP1-RS/RBP1L-RS ratio that are observed during development. These results provide the first example of a feedback-regulated SR protein network with evidence of an active homeostatic role for alternative isoforms.