hnRNP K interacts with RNA binding motif protein 42 and functions in the maintenance of cellular ATP level during stress conditions
hnRNP K interacts with RNA binding motif protein 42 and functions in the maintenance of cellular ATP level during stress conditions
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DOI：
10.1111/j.1365-2443.2008.01256.x
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发表时间：
2009-02-01
期刊：
影响因子：
2.1
通讯作者：
Irie, Kenji
中科院分区：
文献类型：
--
作者：
Fukuda, Toshiyuki;Naiki, Takahiro;Irie, Kenji
异质性核核糖核蛋白K（hnRNP K）是一种保守的RNA结合蛋白，与多种分子伴侣一起参与基因表达的多个过程，包括染色质重塑、转录、RNA剪接、mRNA稳定性和翻译。在这里，我们确定了一个以前未知的蛋白质RNA结合基序蛋白42（RBM 42）作为hnRNP K-结合蛋白。在体内和体外，RBM 42直接与hnRNPK结合。RBM 42还直接结合到p21 mRNA的3'非翻译区，p21 mRNA是hnRNPK的靶mRNA之一。RBM 42主要定位在细胞核内，并与hnRNP K共定位在那里。当细胞用嘌呤霉素、山梨醇或亚砷酸盐处理时，其诱导形成应激颗粒（SGs），停滞的翻译前起始复合物的细胞质聚集体，hnRNP K和RBM 42都定位于SGs。通过RNA干扰耗尽hnRNP K降低了从应激条件释放后的细胞ATP水平。RBM 42与hnRNP K的同时耗竭增强了hnRNP K耗竭的效果。我们的研究结果表明，hnRNP K和RBM 42是SGs的组成部分，并表明hnRNP K和RBM 42可能通过保护其靶mRNA而在应激条件下维持细胞ATP水平。
Heterogeneous nuclear ribonucleoprotein K (hnRNP K) is a conserved RNA-binding protein that is involved in multiple processes of gene expression, including chromatin remodeling, transcription, RNA splicing, mRNA stability and translation, together with diverse groups of molecular partners. Here we identified a previously uncharacterized protein RNA binding motif protein 42 (RBM42) as hnRNP K-binding protein. RBM42 directly bound to hnRNP K in vivo and in vitro. RBM42 also directly bound to the 3' untranslated region of p21 mRNA, one of the target mRNAs for hnRNP K. RBM42 predominantly localized within the nucleus and co-localized with hnRNP K there. When cells were treated with agents, puromycin, sorbitol or arsenite, which induced the formation of stress granules (SGs), cytoplasmic aggregates of stalled translational pre-initiation complexes, both hnRNP K and RBM42 localized at SGs. Depletion of hnRNP K by RNA interference decreased cellular ATP level following release from stress conditions. Simultaneous depletion of RBM42 with hnRNP K enhanced the effect of the hnRNP K depletion. Our results indicate that hnRNP K and RBM42 are components of SGs and suggest that hnRNP K and RBM42 have a role in the maintenance of cellular ATP level in the stress conditions possibly through protecting their target mRNAs.