A role for transportin in deposition of TTP to cytoplasmic RNA granules and mRNA decay.

A role for transportin in deposition of TTP to cytoplasmic RNA granules and mRNA decay.
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DOI:
10.1093/nar/gkp717
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发表时间:
2009-10
影响因子:
14.9
通讯作者:
Tarn WY
Tarn WY
中科院分区:
生物学2区
文献类型:
--
作者:
Chang WL;Tarn WY

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输入蛋白-β家族成员在细胞核和细胞质之间穿梭,对大分子的核胞质运输至关重要。我们试图探究输入蛋白-β家族蛋白是否会随着环境变化而改变其细胞定位。在本报告中,我们发现在正常细胞条件下,转运蛋白(TRN)在细胞质加工体(p -体)中检测到的含量最低,但在应激细胞中,转运蛋白(TRN)大部分转移到应激颗粒(SGs)中。光漂白分析后的荧光恢复表明TRN在胞质颗粒中快速进出。TRN的消耗大大促进了p -小体的形成,但不影响SGs的数量和大小,这表明TRN或其货物参与了p -小体的细胞功能。因此,TRN与三曲霉氨酸(TTP)及其富含au元素(ARE)的mRNA底物相关。通过敲除5 ‘ -3 ’外切酶Xrn1观察到,TRN的缺失增加了p小体的数量并稳定了含are的mrna。此外,TRN的消耗保留了p体中的TTP,同时降低了移动TTP到SGs的比例。因此,我们的数据共同表明,TRN在细胞质颗粒之间的TTP运输中发挥作用,从而调节含are mrna的稳定性。
Importin-β family members, which shuttle between the nucleus and the cytoplasm, are essential for nucleocytoplasmic transport of macromolecules. We attempted to explore whether importin-β family proteins change their cellular localization in response to environmental change. In this report, we show that transportin (TRN) was minimally detected in cytoplasmic processing bodies (P-bodies) under normal cell conditions but largely translocated to stress granules (SGs) in stressed cells. Fluorescence recovery after photobleaching analysis indicated that TRN moves rapidly in and out of cytoplasmic granules. Depletion of TRN greatly enhanced P-body formation but did not affect the number or size of SGs, suggesting that TRN or its cargo(es) participates in cellular function of P-bodies. Accordingly, TRN associated with tristetraprolin (TTP) and its AU-rich element (ARE)-containing mRNA substrates. Depletion of TRN increased the number of P-bodies and stabilized ARE-containing mRNAs, as observed with knockdown of the 5′–3′ exonuclease Xrn1. Moreover, depletion of TRN retained TTP in P-bodies and meanwhile reduced the fraction of mobile TTP to SGs. Therefore, our data together suggest that TRN plays a role in trafficking of TTP between the cytoplasmic granules and whereby modulates the stability of ARE-containing mRNAs.
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