Free mRNA in excess upon polysome dissociation is a scaffold for protein multimerization to form stress granules.
Free mRNA in excess upon polysome dissociation is a scaffold for protein multimerization to form stress granules.
复制标题
多核体解离时过量的自由mRNA是蛋白质多聚化的支架，形成应激颗粒。
DOI：
10.1093/nar/gku582
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发表时间：
2014-07
影响因子：
14.9
通讯作者：
Pastré D
中科院分区：
文献类型：
--
作者：
Bounedjah O;Desforges B;Wu TD;Pioche-Durieu C;Marco S;Hamon L;Curmi PA;Guerquin-Kern JL;Piétrement O;Pastré D
导致应激细胞中应激颗粒组装的事件序列仍然难以捉摸。我们在这里表明，使用同位素标记和离子探针，按比例更多的RNA比蛋白质存在于应力颗粒比周围的细胞质。我们进一步证明，单链多核苷酸，mRNA和ssDNA，到细胞质的交付可以触发应力颗粒组装。另一方面，增加mRNA结合蛋白质如YB-1的细胞质水平可以通过形成分离的mRNP直接阻止mRNA的聚集，如原子力显微镜所证明的。有趣的是，我们还发现去核细胞确实形成了应激颗粒，这表明像TIA-1这样的核朊病毒样RNA结合蛋白易位到细胞质中是应激颗粒组装的关键。这些结果导致了基于以下事件序列的关于应激颗粒形成的另一种观点：在应激期间多聚核糖体大量解离后，非多聚核糖体mRNA的爆发超过了mRNA稳定蛋白如YB-1。因此，脱离核糖体的mRNA变得易于与mRNA结合的易聚集蛋白或错误折叠蛋白接触，从而诱导应激颗粒形成。在这个模型的框架内，穿梭的核mRNA稳定蛋白质的细胞质可以解离应力颗粒或阻止其组装。
The sequence of events leading to stress granule assembly in stressed cells remains elusive. We show here, using isotope labeling and ion microprobe, that proportionally more RNA than proteins are present in stress granules than in surrounding cytoplasm. We further demonstrate that the delivery of single strand polynucleotides, mRNA and ssDNA, to the cytoplasm can trigger stress granule assembly. On the other hand, increasing the cytoplasmic level of mRNA-binding proteins like YB-1 can directly prevent the aggregation of mRNA by forming isolated mRNPs, as evidenced by atomic force microscopy. Interestingly, we also discovered that enucleated cells do form stress granules, demonstrating that the translocation to the cytoplasm of nuclear prion-like RNA-binding proteins like TIA-1 is dispensable for stress granule assembly. The results lead to an alternative view on stress granule formation based on the following sequence of events: after the massive dissociation of polysomes during stress, mRNA-stabilizing proteins like YB-1 are outnumbered by the burst of nonpolysomal mRNA. mRNA freed of ribosomes thus becomes accessible to mRNA-binding aggregation-prone proteins or misfolded proteins, which induces stress granule formation. Within the frame of this model, the shuttling of nuclear mRNA-stabilizing proteins to the cytoplasm could dissociate stress granules or prevent their assembly.
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DOI：
10.1016/s0006-291x(03)01318-4
发表时间：
2003-08-15
影响因子：
3.1
作者：
Jammi, NV;Whitby, LR;Beal, PA
通讯作者：
Beal, PA
影响因子：
4.2
作者：
Gal J;Zhang J;Kwinter DM;Zhai J;Jia H;Jia J;Zhu H
通讯作者：
Zhu H
影响因子：
3.7
作者：
De Leeuw, Frederic;Zhang, Tong;Gueydan, Cyril
通讯作者：
Gueydan, Cyril
影响因子：
5.3
作者：
Evdokimova, V;Ruzanov, P;Sorensen, PHB
通讯作者：
Sorensen, PHB
影响因子：
3.9
作者：
Ivanov, PA;Chudinova, EM;Nadezhdina, ES
通讯作者：
Nadezhdina, ES