A truncated hnRNP A1 isoform, lacking the RGG-box RNA binding domain, can efficiently regulate HIV-1 splicing and replication.
A truncated hnRNP A1 isoform, lacking the RGG-box RNA binding domain, can efficiently regulate HIV-1 splicing and replication.
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DOI：
10.1016/j.bbagrm.2014.02.002
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发表时间：
2014
影响因子：
4.7
通讯作者：
Caputi, Massimo
中科院分区：
文献类型：
--
作者：
Jean-Philippe, Jacques;Paz, Sean;Lu, Michael L.;Caputi, Massimo
异质核核糖核蛋白A1（hnRNPA 1）是最丰富的RNA结合蛋白之一。hnRNP A1主要定位于细胞核内，但它可以响应于在细胞核和细胞质之间穿梭的特定刺激而重新定位到细胞质。该蛋白的细胞定位由短的C-末端基序（M9）和其他不太确定的序列调节。该蛋白的RNA结合特异性依赖于多个RNA结合结构域（RBD），其调节其在RNA加工和表达中的作用。hnRNP A1通过调节信使RNA的生物合成和翻译、miRNA的加工、影响转录和控制端粒的维持在基因表达中发挥多种作用。这种蛋白质的多种功能与遗传疾病、癌症和病毒病原体复制中的不同作用相关。利用标记的hnRNP A1缺失文库，我们已经表明，三个hnRNP A1 RBD有助于蛋白质的普遍核分布。我们的数据还表明，截短形式的蛋白质，缺乏一个RBD，RGG盒，可以调节剪接的报告基因的剪接和下调HIV-1病毒的复制与野生型蛋白质的效率相当。该功能性hnRNP A1缺失突变体类似于预测的hnRNP A1同种型，其先前未被实验表征。
Heterogeneous nuclear ribonucleoprotein A1 (hnRNP A1) is one of the most abundant RNA binding proteins. hnRNP A1 is localized prevalently in the nucleus but it can relocate to the cytoplasm in response to specific stimuli shuttling between nuclear and cytoplasmic compartments. The cellular localization of this protein is regulated by a short C-terminus motif (M9) and other less defined sequences. The RNA binding specificity of this protein is dependent on multiple RNA binding domains (RBDs), which regulate its role in RNA processing and expression. hnRNP A1 plays multiple roles in gene expression by regulating the biogenesis and translation of messengers RNAs, the processing of miRNAs, affecting transcription and controlling telomere maintenance. The multiple functions of this protein correlate with diverse roles in genetic disease, cancer and the replication of viral pathogens. Utilizing a tagged hnRNP A1 deletion library we have shown that the three hnRNP A1 RBDs contribute to the prevalent nuclear distribution of the protein. Our data also indicate that a truncated form of the protein, lacking one of the RBDs, the RGG-box, can regulate splicing of a splicing reporter minigene and down-regulate replication of the HIV-1 virus with efficiency comparable to the wild type protein. This functional hnRNP A1 deletion mutant is similar to a predicted hnRNP A1 isoform, which had not been previously experimentally characterized.
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DOI：
10.1007/s00018-008-8532-1
发表时间：
2009-04
期刊：
Cellular and molecular life sciences : CMLS
影响因子：
--
作者：
He Y;Smith R
通讯作者：
Smith R
影响因子：
4.5
作者：
Mayeda, A;Munroe, SH;Krainer, AR
通讯作者：
Krainer, AR
影响因子：
5.6
作者：
Jean-Philippe J;Paz S;Caputi M
通讯作者：
Caputi M
影响因子：
11.4
作者：
MAYEDA, A;MUNROE, SH;KRAINER, AR
通讯作者：
KRAINER, AR
影响因子：
64.5
作者：
BERKHOUT, B;SILVERMAN, RH;JEANG, KT
通讯作者：
JEANG, KT