Genome-wide Survey of Ribosome Collision.

Genome-wide Survey of Ribosome Collision.
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核糖体碰撞的全基因组调查。

DOI:
10.1016/j.celrep.2020.107610
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发表时间:
2020-05-05
期刊:
影响因子:
8.8
通讯作者:
Iwasaki S
Iwasaki S
中科院分区:
生物学1区
文献类型:
--
作者:
Han P;Shichino Y;Schneider-Poetsch T;Mito M;Hashimoto S;Udagawa T;Kohno K;Yoshida M;Mishima Y;Inada T;Iwasaki S

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核糖体的运动并不总是顺利的,而且经常受到阻碍。对于核糖体的停顿,基本问题仍有待解决,包括核糖体在mrna上停顿的位置,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衰减的生理意义。在这里,我们使用改进的核糖体分析方法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,出现在不同的位点:Pro-Pro/Gly/Asp基序;Arg-X-Lys图案;停止密码子;还有3 '未翻译区。带电新生链和核糖体出口通道之间的静电相互作用决定了eif5a介导的Pro-Pro位点二体的拯救。特别是,内质网(ER)应激反应转录因子的前体XBP1u显示出惊人的碰撞核糖体队列,因此通过核糖体相关的质量控制作为降解底物。我们的研究结果通过解剖碰撞核糖体提供了对核糖体暂停的原因和后果的深入了解。Han等人通过对人类和斑马鱼的二体足迹进行测序,调查了整个转录组中的核糖体碰撞位点,发现核糖体的延伸、终止和循环的低效率环境有助于核糖体的碰撞。他们还发现XBP1u是核糖体相关质量控制的内源性靶标。
Ribosome movement is not always smooth and is rather often impeded. For ribosome pauses, fundamental issues remain to be addressed, including where ribosomes pause on mRNAs, what kind of RNA/amino acid sequence causes this pause, and the physiological significance of this attenuation of protein synthesis. Here, we survey the positions of ribosome collisions caused by ribosome pauses in humans and zebrafish using modified ribosome profiling. Collided ribosomes, i.e., disomes, emerge at various sites: Pro-Pro/Gly/Asp motifs; Arg-X-Lys motifs; stop codons; and 3’ untranslated regions. The electrostatic interaction between the charged nascent chain and the ribosome exit tunnel determines the eIF5A-mediated disome rescue at the Pro-Pro sites. In particular, XBP1u, a precursor of endoplasmic reticulum (ER)-stress-responsive transcription factor, shows striking queues of collided ribosomes and thus acts as a degradation substrate by ribosome-associated quality control. Our results provide insight into the causes and consequences of ribosome pause by dissecting collided ribosomes. Han et al. survey ribosome collision sites across the transcriptome by sequencing disome footprints in humans and zebrafish and find that inefficient contexts for elongation, termination, and recycling of ribosomes contributes to the collision of ribosomes. They also uncover XBP1u as an endogenous target of ribosome-associated quality control.
DOI: 10.1371/journal.pbio.1001508
发表时间: 2013
期刊: PLoS biology
影响因子: 9.8
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