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4EHP and GIGYF1/2 Mediate Translation-Coupled Messenger RNA Decay

71 Pages Posted: 10 Mar 2020 Sneak Peek Status: Review Complete

See all articles by Ramona Weber

Ramona Weber

Max Planck Institute for Developmental Biology - Department of Biochemistry

Min-Yi Chung

Max Planck Institute for Developmental Biology - Department of Biochemistry

Ulrike Zinnall

Helmholtz Association of German Research Centres - Berlin Institute for Medical Systems Biology

Markus Landthaler

Helmholtz Association of German Research Centres - Berlin Institute for Medical Systems Biology

Eugene Valkov

Max Planck Institute for Developmental Biology - Department of Biochemistry

Elisa Izaurralde

Max Planck Institute for Developmental Biology - Department of Biochemistry

Catia Igreja

Max Planck Institute for Developmental Biology - Department of Biochemistry

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Abstract

Current models of mRNA turnover indicate that cytoplasmic degradation is coupled with translation. However, our understanding of the molecular events that coordinate ribosome transit with the mRNA decay machinery is still limited. Here, we show that the 4EHP–GIGYF1/2 complexes trigger co-translational mRNA decay as a result of perturbed elongation. Human cells lacking 4EHP and GIGYF1/2 proteins accumulate transcripts known to be degraded in a translation-dependent manner or with prominent ribosome pausing. These include among others, mRNAs encoding secretory and membrane-bound proteins or α- and β-tubulin subunits. In addition, 4EHP–GIGYF1/2 complexes fail to reduce target mRNA levels in the absence of ribosome stalling or upon disruption of their interaction with the mRNA cap structure, DDX6 or GYF domain-associated factors. Our studies reveal how a repressor complex linked to neurological disorders minimizes the protein output of a subset of mRNAs.

Keywords: mRNA decay, translation, ribosome pausing, DDX6, GYF domain, endoplasmic reticulum, tubulin

Suggested Citation

Weber, Ramona and Chung, Min-Yi and Zinnall, Ulrike and Landthaler, Markus and Valkov, Eugene and Izaurralde, Elisa and Igreja, Catia, 4EHP and GIGYF1/2 Mediate Translation-Coupled Messenger RNA Decay. Available at SSRN: https://ssrn.com/abstract=3548260 or http://dx.doi.org/10.2139/ssrn.3548260
This is a paper under consideration at Cell Press and has not been peer-reviewed.

Ramona Weber

Max Planck Institute for Developmental Biology - Department of Biochemistry ( email )

Max-PlanckRing 5
Tübingen, D-72076
Germany

Min-Yi Chung

Max Planck Institute for Developmental Biology - Department of Biochemistry

Max-PlanckRing 5
Tübingen, D-72076
Germany

Ulrike Zinnall

Helmholtz Association of German Research Centres - Berlin Institute for Medical Systems Biology

Anna-Louisa-Karsch-Straße 2
Robert-Rössle-Str. 10
Berlin, Berlin 10178
United States

Markus Landthaler

Helmholtz Association of German Research Centres - Berlin Institute for Medical Systems Biology

Anna-Louisa-Karsch-Straße 2
Robert-Rössle-Str. 10
Berlin, Berlin 10178
United States

Eugene Valkov

Max Planck Institute for Developmental Biology - Department of Biochemistry

Max-PlanckRing 5
Tübingen, D-72076
Germany

Elisa Izaurralde

Max Planck Institute for Developmental Biology - Department of Biochemistry

Max-PlanckRing 5
Tübingen, D-72076
Germany

Catia Igreja (Contact Author)

Max Planck Institute for Developmental Biology - Department of Biochemistry ( email )

Max-PlanckRing 5
Tübingen, D-72076
Germany

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