mRNA stem-loops can pause the ribosome by hindering A-site tRNA binding (Elife. 2020, 9:e55799)

報告日期: 2020/12/08
報告時間: 16:00/16:50
報告學生: 黃馨霈(英文報告)
講評老師: 吳尚蓉
附件下載:

mRNA stem-loops can pause the ribosome by hindering A-site tRNA binding

Chen Bao, Sarah Loerch, Clarence Ling, Andrei A Korostelev, Nikolaus Grigorieff Is a corresponding author, Dmitri N Ermolenko  DOI: 10.7554/eLife.55799

Speaker: Hsin-Pei Huang                     Commentator: Shang-Rung Wu

Date: 8th December, 2020

Abstract:

Programmed ribosomal frameshifting (PRF) is a translational recoding phenomenon, during PRF, ribosome would be paused and shift to an alternative frame. This recoding strategy is important for virus replication and involves in mRNA no-go decay and gene expression controlling. In the past, there were studies try to reveal the mechanism of PRF, but the details are still unclear. Generally, PRF is known what ribosome is paused by downstream mRNA structure or other obstacles. Before ribosomal helicase unwinding the mRNA structure, ribosome would slip on slippery sequence. Hence, the shifting is usually correlated to the stability of downstream mRNA structure. However, the data show that ribosome paused by the frameshift stimulating sequence (FSS) itself rather than the stability of FSS.

In recent years, as cryo-EM broke the barrier of resolution as well as reached 3 Å resolution or even better, more and more researchers used cryo-EM to be the tool for investigating the details of PRF mechanism. Combining smFRET and cryo-EM, this study gives a new sight of frameshifting, the FSS inhibited the rotation of ribosome and decreased the A-site tRNA decoding efficiency. Moreover, the cryo-EM model shows that mRNA stem-loop occupied the A-site space and therefore the entrance of A-site tRNA was blocked.

To sum up, there is an alternative way, which differs from the way we have known, can make PRF occur, and the discovery gives a new sight to understand PRF.

Reference:

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Kim, Hee-Kyung, et al. "A frameshifting stimulatory stem loop destabilizes the hybrid state and impedes ribosomal translocation." Proceedings of the National Academy of Sciences 111.15 (2014): 5538-5543.

Yusupova, Gulnara Zh, et al. "The path of messenger RNA through the ribosome." Cell 106.2 (2001): 233-241.

Zhang, Yan, et al. "Alternative mode of E-site tRNA binding in the presence of a downstream mRNA stem loop at the entrance channel." Structure 26.3 (2018): 437-445.