PT  - JOURNAL ARTICLE
AU  - Peixun Han
AU  - Mari Mito
AU  - Yuichi Shichino
AU  - Satoshi Hashimoto
AU  - Tsuyoshi Udagawa
AU  - Kenji Kohno
AU  - Yuichiro Mishima
AU  - Toshifumi Inada
AU  - Shintaro Iwasaki
TI  - Genome-wide survey of ribosome collision
AID  - 10.1101/710491
DP  - 2019 Jan 01
TA  - bioRxiv
PG  - 710491
4099  - http://biorxiv.org/content/early/2019/07/22/710491.short
4100  - http://biorxiv.org/content/early/2019/07/22/710491.full
AB  - 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.