Kinesin transports RNA: Isolation and characterization of an RNA-transporting granule

Kinesin transports RNA: Isolation and characterization of an RNA-transporting granule
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DOI:
10.1016/j.neuron.2004.07.022
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发表时间:
2004-08-19
期刊:
影响因子:
16.2
通讯作者:
Hirokawa, N
Hirokawa, N
中科院分区:
医学1区
文献类型:
--
作者:
Kanai, Y;Dohmae, N;Hirokawa, N

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RNA转运是局部蛋白质合成的一个重要且基本的事件,尤其是在神经元中。RNA是以大颗粒的形式被转运的,但人们对其知之甚少。在此,我们分离出了一个大的核糖核酸酶敏感颗粒(大小约为1000S),它是常规驱动蛋白(KIF5)的结合伴侣。我们在该颗粒中鉴定出了总共42种蛋白质以及CaMKIIα和Arc的mRNA。对其中17种蛋白质(hnRNP - U、Purα和β、PSF、DDX1、DDX3、SYNCRIP、TLS、NonO、HSPC117、ALY、CGI - 99、staufen、三种FMRP以及EF - 1α)进行了广泛研究,包括它们的分类、结合组合以及对RNA“转运”的必要性。这些蛋白质和mRNA共定位在树突中与驱动蛋白相关的颗粒上。这些颗粒双向移动,KIF5的过表达会增强其向远端的移动,而其功能受阻则会减弱这种移动。因此,驱动蛋白通过这种颗粒在树突中与诸如动力蛋白等相反的马达协同转运RNA。
RNA transport is an important and fundamental event for local protein synthesis, especially in neurons. RNA is transported as large granules, but little is known about them. Here, we isolated a large RNase-sensitive granule (size: 1000Ssimilar to) as a binding partner of conventional kinesin (KIF5). We identified a total of 42 proteins with mRNAs for CaMKIIalpha and Arc in the granule. Seventeen of the proteins (hnRNP-U, Pur alpha and beta, PSF, DDX1, DDX3, SYNCRIP, TLS, NonO, HSPC117, ALY, CGI-99, staufen, three FMRPs, and EF-1alpha) were extensively investigated, including their classification, binding combinations, and necessity for the "transport" of RNA. These proteins and the mRNAs were colocalized to the kinesin-associated granules in dendrites. The granules moved bidirectionally, and the distally directed movement was enhanced by the overexpression of KIF5 and reduced by its functional blockage. Thus, kinesin transports RNA via this granule in dendrites coordinately with opposite motors, such as dynein.