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Genome-wide survey of ribosome collision

Peixun Han, Mari Mito, View ORCID ProfileYuichi Shichino, Satoshi Hashimoto, Tsuyoshi Udagawa, View ORCID ProfileKenji Kohno, View ORCID ProfileYuichiro Mishima, View ORCID ProfileToshifumi Inada, View ORCID ProfileShintaro Iwasaki
doi: https://doi.org/10.1101/710491
Peixun Han
1Department of Computational Biology and Medical Sciences, Graduate School of Frontier Sciences, The University of Tokyo, Kashiwa, Chiba 277-8561, Japan
2RNA Systems Biochemistry Laboratory, RIKEN Cluster for Pioneering Research, Wako, Saitama 351-0198, Japan
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Mari Mito
2RNA Systems Biochemistry Laboratory, RIKEN Cluster for Pioneering Research, Wako, Saitama 351-0198, Japan
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Yuichi Shichino
2RNA Systems Biochemistry Laboratory, RIKEN Cluster for Pioneering Research, Wako, Saitama 351-0198, Japan
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Satoshi Hashimoto
3Graduate School of Pharmaceutical Sciences, Tohoku University, Sendai, Miyagi 980-8578, Japan
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Tsuyoshi Udagawa
3Graduate School of Pharmaceutical Sciences, Tohoku University, Sendai, Miyagi 980-8578, Japan
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Kenji Kohno
4Graduate School of Biological Sciences and Institute for Research Initiatives, Nara Institute of Science and Technology, Ikoma, Nara 630-0192, Japan
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  • ORCID record for Kenji Kohno
Yuichiro Mishima
5Faculty of Life Sciences, Kyoto Sangyo University, Kita-ku, Kyoto 603-8555, Japan
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Toshifumi Inada
3Graduate School of Pharmaceutical Sciences, Tohoku University, Sendai, Miyagi 980-8578, Japan
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Shintaro Iwasaki
1Department of Computational Biology and Medical Sciences, Graduate School of Frontier Sciences, The University of Tokyo, Kashiwa, Chiba 277-8561, Japan
2RNA Systems Biochemistry Laboratory, RIKEN Cluster for Pioneering Research, Wako, Saitama 351-0198, Japan
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  • ORCID record for Shintaro Iwasaki
  • For correspondence: shintaro.iwasaki@riken.jp
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Abstract

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.

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Posted July 22, 2019.
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Genome-wide survey of ribosome collision
Peixun Han, Mari Mito, Yuichi Shichino, Satoshi Hashimoto, Tsuyoshi Udagawa, Kenji Kohno, Yuichiro Mishima, Toshifumi Inada, Shintaro Iwasaki
bioRxiv 710491; doi: https://doi.org/10.1101/710491
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Genome-wide survey of ribosome collision
Peixun Han, Mari Mito, Yuichi Shichino, Satoshi Hashimoto, Tsuyoshi Udagawa, Kenji Kohno, Yuichiro Mishima, Toshifumi Inada, Shintaro Iwasaki
bioRxiv 710491; doi: https://doi.org/10.1101/710491

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