Genome-wide survey of ribosome collision
Genome-wide survey of ribosome collision
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DOI：
10.1101/710491
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发表时间：
2019-07
期刊：
影响因子：
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通讯作者：
Peixun Han;M. Mito;Yuichi Shichino;S. Hashimoto;T. Udagawa;K. Kohno;Yuichiro Mishima;T. Inada;Shintaro Iwasaki
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文献类型：
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作者：
Peixun Han;M. Mito;Yuichi Shichino;S. Hashimoto;T. Udagawa;K. Kohno;Yuichiro Mishima;T. Inada;Shintaro Iwasaki
在蛋白质合成中，核糖体的运动并不总是顺利的，而且由于许多原因而经常受到阻碍。尽管核糖体的减速决定了mrna和蛋白质合成的命运，但仍有一些基本问题有待解决，包括核糖体在mrna中的停顿位置，什么样的RNA/氨基酸序列导致这种停顿，以及这种蛋白质合成放缓的生理意义。在这里，我们使用改良的核糖体分析在全基因组水平上调查了人类和斑马鱼中由核糖体暂停引起的核糖体碰撞的位置。碰撞核糖体，即二体，出现在不同的位置：脯氨酸-脯氨酸-赖氨酸基序，停止密码子和3 '未翻译区（UTR）。参与碰撞的核糖体数量不限于两个，而是四到五个核糖体可以形成一个核糖体队列。特别是，未折叠蛋白反应的关键调节剂XBP1显示出碰撞核糖体的惊人队列，因此作为核糖体相关质量控制（RQC）的底物，以避免在没有压力的情况下不需要的蛋白质的积累。我们的研究结果通过剖析核糖体的特定结构提供了对核糖体减速的原因和后果的深入了解。
In protein synthesis, ribosome movement is not always smooth and is rather often impeded for numerous reasons. Although the deceleration of the ribosome defines the fates of the mRNAs and synthesizing proteins, fundamental issues remain to be addressed, including where ribosomes pause in mRNAs, what kind of RNA/amino acid sequence causes this pause, and the physiological significance of this slowdown of protein synthesis. Here, we surveyed the positions of ribosome collisions caused by ribosome pausing in humans and zebrafish on a genome-wide level using modified ribosome profiling. The collided ribosomes, i.e., disomes, emerged at various sites: the proline-proline-lysine motif, stop codons, and the 3′ untranslated region (UTR). The number of ribosomes involved in a collision is not limited to two, but rather four to five ribosomes can form a queue of ribosomes. In particular, XBP1, a key modulator of the unfolded protein response, shows striking queues of collided ribosomes and thus acts as a substrate for ribosome-associated quality control (RQC) to avoid the accumulation of undesired proteins in the absence of stress. Our results provide an insight into the causes and consequences of ribosome slowdown by dissecting the specific architecture of ribosomes.