Translation of zinc finger domains induces ribosome collision and Znf598-dependent mRNA decay in zebrafish.

Quality control of translation is crucial for maintaining cellular and organismal homeostasis. Obstacles in translation elongation induce ribosome collision, which is monitored by multiple sensor mechanisms in eukaryotes. The E3 ubiquitin ligase Znf598 recognizes collided ribosomes, triggering ribos...

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Main Authors: Kota Ishibashi, Yuichi Shichino, Peixun Han, Kimi Wakabayashi, Mari Mito, Toshifumi Inada, Seisuke Kimura, Shintaro Iwasaki, Yuichiro Mishima
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2024-12-01
Series:PLoS Biology
Online Access:https://doi.org/10.1371/journal.pbio.3002887
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author Kota Ishibashi
Yuichi Shichino
Peixun Han
Kimi Wakabayashi
Mari Mito
Toshifumi Inada
Seisuke Kimura
Shintaro Iwasaki
Yuichiro Mishima
author_facet Kota Ishibashi
Yuichi Shichino
Peixun Han
Kimi Wakabayashi
Mari Mito
Toshifumi Inada
Seisuke Kimura
Shintaro Iwasaki
Yuichiro Mishima
author_sort Kota Ishibashi
collection DOAJ
description Quality control of translation is crucial for maintaining cellular and organismal homeostasis. Obstacles in translation elongation induce ribosome collision, which is monitored by multiple sensor mechanisms in eukaryotes. The E3 ubiquitin ligase Znf598 recognizes collided ribosomes, triggering ribosome-associated quality control (RQC) to rescue stalled ribosomes and no-go decay (NGD) to degrade stall-prone mRNAs. However, the impact of RQC and NGD on maintaining the translational homeostasis of endogenous mRNAs has remained unclear. In this study, we investigated the endogenous substrate mRNAs of NGD during the maternal-to-zygotic transition (MZT) of zebrafish development. RNA-Seq analysis of zebrafish znf598 mutant embryos revealed that Znf598 down-regulates mRNAs encoding the C2H2-type zinc finger domain (C2H2-ZF) during the MZT. Reporter assays and disome profiling indicated that ribosomes stall and collide while translating tandem C2H2-ZFs, leading to mRNA degradation by Znf598. Our results suggest that NGD maintains the quality of the translatome by mitigating the risk of ribosome collision at the abundantly present C2H2-ZF sequences in the vertebrate genome.
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spelling doaj-art-0068dcfa1ef74ec4a9a6a868836cf0162025-08-20T01:54:38ZengPublic Library of Science (PLoS)PLoS Biology1544-91731545-78852024-12-012212e300288710.1371/journal.pbio.3002887Translation of zinc finger domains induces ribosome collision and Znf598-dependent mRNA decay in zebrafish.Kota IshibashiYuichi ShichinoPeixun HanKimi WakabayashiMari MitoToshifumi InadaSeisuke KimuraShintaro IwasakiYuichiro MishimaQuality control of translation is crucial for maintaining cellular and organismal homeostasis. Obstacles in translation elongation induce ribosome collision, which is monitored by multiple sensor mechanisms in eukaryotes. The E3 ubiquitin ligase Znf598 recognizes collided ribosomes, triggering ribosome-associated quality control (RQC) to rescue stalled ribosomes and no-go decay (NGD) to degrade stall-prone mRNAs. However, the impact of RQC and NGD on maintaining the translational homeostasis of endogenous mRNAs has remained unclear. In this study, we investigated the endogenous substrate mRNAs of NGD during the maternal-to-zygotic transition (MZT) of zebrafish development. RNA-Seq analysis of zebrafish znf598 mutant embryos revealed that Znf598 down-regulates mRNAs encoding the C2H2-type zinc finger domain (C2H2-ZF) during the MZT. Reporter assays and disome profiling indicated that ribosomes stall and collide while translating tandem C2H2-ZFs, leading to mRNA degradation by Znf598. Our results suggest that NGD maintains the quality of the translatome by mitigating the risk of ribosome collision at the abundantly present C2H2-ZF sequences in the vertebrate genome.https://doi.org/10.1371/journal.pbio.3002887
spellingShingle Kota Ishibashi
Yuichi Shichino
Peixun Han
Kimi Wakabayashi
Mari Mito
Toshifumi Inada
Seisuke Kimura
Shintaro Iwasaki
Yuichiro Mishima
Translation of zinc finger domains induces ribosome collision and Znf598-dependent mRNA decay in zebrafish.
PLoS Biology
title Translation of zinc finger domains induces ribosome collision and Znf598-dependent mRNA decay in zebrafish.
title_full Translation of zinc finger domains induces ribosome collision and Znf598-dependent mRNA decay in zebrafish.
title_fullStr Translation of zinc finger domains induces ribosome collision and Znf598-dependent mRNA decay in zebrafish.
title_full_unstemmed Translation of zinc finger domains induces ribosome collision and Znf598-dependent mRNA decay in zebrafish.
title_short Translation of zinc finger domains induces ribosome collision and Znf598-dependent mRNA decay in zebrafish.
title_sort translation of zinc finger domains induces ribosome collision and znf598 dependent mrna decay in zebrafish
url https://doi.org/10.1371/journal.pbio.3002887
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