A novel role for shuttling SR proteins in mRNA translation
A novel role for shuttling SR proteins in mRNA translation
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DOI：
10.1101/gad.286404
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发表时间：
2004-04-01
影响因子：
10.5
通讯作者：
Cáceres, JF
中科院分区：
文献类型：
--
作者：
Sanford, JR;Gray, NK;Cáceres, JF
富含Ser-Arg(SR)的蛋白质组成了一个核磷蛋白大家族，是结构性剪接和选择性剪接所必需的。SR蛋白的一个子集在细胞核和细胞质之间连续穿梭，这表明穿梭SR蛋白在基因表达中的作用可能不仅限于核前mRNA剪接，还可能包括未知的细胞质功能。在这里，我们证明了穿梭SR蛋白，特别是SF2/ASF，与翻译核糖体相关，并在非洲爪哇卵母细胞中与报告mRNA捆绑在一起时刺激翻译。此外，SF2/ASF增强了报告基因在HeLa细胞中的翻译，这一活性依赖于其从细胞核到细胞质的穿梭能力，并因外显子剪接增强子的存在而增加。此外，SF2/ASF可以利用HeLa无细胞翻译系统刺激体外翻译。因此，SR蛋白与翻译核糖体的联系，以及体内和体外翻译的刺激，强烈表明SR蛋白在翻译中的穿梭作用。我们提出了穿梭SR蛋白在真核基因转录后表达中的多种作用，并说明了它们如何耦合剪接和翻译。
The Ser-Arg-rich (SR) proteins comprise a large family of nuclear phosphoproteins that are required for constitutive and alternative splicing. A subset of SR proteins shuttles continuously between the nucleus and the cytoplasm, suggesting that the role of shuttling SR proteins in gene expression may not be limited to nuclear pre-mRNA splicing, but may also include unknown cytoplasmic functions. Here, we show that shuttling SR proteins, in particular SF2/ASF, associate with translating ribosomes and stimulate translation when tethered to a reporter mRNA in Xenopus oocytes. Moreover, SF2/ASF enhances translation of reporter mRNAs in HeLa cells, and this activity is dependent on its ability to shuttle from the nucleus to the cytoplasm and is increased by the presence of an exonic-splicing enhancer. Furthermore, SF2/ASF can stimulate translation in vitro using a HeLa cell-free translation system. Thus, the association of SR proteins with translating ribosomes, as well as the stimulation of translation both in vivo and in vitro, strongly suggest a role for shuttling SR proteins in translation. We propose that shuttling SR proteins play multiple roles in the posttranscriptional expression of eukaryotic genes and illustrate how they may couple splicing and translation.