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Autogenous cross-regulation of Quaking mRNA processing and translation balances Quaking functions in splicing and translation

Quaking protein isoforms arise from a single Quaking gene and bind the same RNA motif to regulate splicing, translation, decay, and localization of a large set of RNAs. However, the mechanisms by which Quaking expression is controlled to ensure that appropriate amounts of each isoform are available...

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Autores principales: Fagg, W. Samuel, Liu, Naiyou, Fair, Jeffrey Haskell, Shiue, Lily, Katzman, Sol, Donohue, John Paul, Ares, Manuel
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Cold Spring Harbor Laboratory Press 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5695090/
https://www.ncbi.nlm.nih.gov/pubmed/29021242
http://dx.doi.org/10.1101/gad.302059.117
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author Fagg, W. Samuel
Liu, Naiyou
Fair, Jeffrey Haskell
Shiue, Lily
Katzman, Sol
Donohue, John Paul
Ares, Manuel
author_facet Fagg, W. Samuel
Liu, Naiyou
Fair, Jeffrey Haskell
Shiue, Lily
Katzman, Sol
Donohue, John Paul
Ares, Manuel
author_sort Fagg, W. Samuel
collection PubMed
description Quaking protein isoforms arise from a single Quaking gene and bind the same RNA motif to regulate splicing, translation, decay, and localization of a large set of RNAs. However, the mechanisms by which Quaking expression is controlled to ensure that appropriate amounts of each isoform are available for such disparate gene expression processes are unknown. Here we explore how levels of two isoforms, nuclear Quaking-5 (Qk5) and cytoplasmic Qk6, are regulated in mouse myoblasts. We found that Qk5 and Qk6 proteins have distinct functions in splicing and translation, respectively, enforced through differential subcellular localization. We show that Qk5 and Qk6 regulate distinct target mRNAs in the cell and act in distinct ways on their own and each other's transcripts to create a network of autoregulatory and cross-regulatory feedback controls. Morpholino-mediated inhibition of Qk translation confirms that Qk5 controls Qk RNA levels by promoting accumulation and alternative splicing of Qk RNA, whereas Qk6 promotes its own translation while repressing Qk5. This Qk isoform cross-regulatory network responds to additional cell type and developmental controls to generate a spectrum of Qk5/Qk6 ratios, where they likely contribute to the wide range of functions of Quaking in development and cancer.
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spelling pubmed-56950902018-03-15 Autogenous cross-regulation of Quaking mRNA processing and translation balances Quaking functions in splicing and translation Fagg, W. Samuel Liu, Naiyou Fair, Jeffrey Haskell Shiue, Lily Katzman, Sol Donohue, John Paul Ares, Manuel Genes Dev Research Paper Quaking protein isoforms arise from a single Quaking gene and bind the same RNA motif to regulate splicing, translation, decay, and localization of a large set of RNAs. However, the mechanisms by which Quaking expression is controlled to ensure that appropriate amounts of each isoform are available for such disparate gene expression processes are unknown. Here we explore how levels of two isoforms, nuclear Quaking-5 (Qk5) and cytoplasmic Qk6, are regulated in mouse myoblasts. We found that Qk5 and Qk6 proteins have distinct functions in splicing and translation, respectively, enforced through differential subcellular localization. We show that Qk5 and Qk6 regulate distinct target mRNAs in the cell and act in distinct ways on their own and each other's transcripts to create a network of autoregulatory and cross-regulatory feedback controls. Morpholino-mediated inhibition of Qk translation confirms that Qk5 controls Qk RNA levels by promoting accumulation and alternative splicing of Qk RNA, whereas Qk6 promotes its own translation while repressing Qk5. This Qk isoform cross-regulatory network responds to additional cell type and developmental controls to generate a spectrum of Qk5/Qk6 ratios, where they likely contribute to the wide range of functions of Quaking in development and cancer. Cold Spring Harbor Laboratory Press 2017-09-15 /pmc/articles/PMC5695090/ /pubmed/29021242 http://dx.doi.org/10.1101/gad.302059.117 Text en © 2017 Fagg et al.; Published by Cold Spring Harbor Laboratory Press http://creativecommons.org/licenses/by-nc/4.0/ This article is distributed exclusively by Cold Spring Harbor Laboratory Press for the first six months after the full-issue publication date (see http://genesdev.cshlp.org/site/misc/terms.xhtml). After six months, it is available under a Creative Commons License (Attribution-NonCommercial 4.0 International), as described at http://creativecommons.org/licenses/by-nc/4.0/.
spellingShingle Research Paper
Fagg, W. Samuel
Liu, Naiyou
Fair, Jeffrey Haskell
Shiue, Lily
Katzman, Sol
Donohue, John Paul
Ares, Manuel
Autogenous cross-regulation of Quaking mRNA processing and translation balances Quaking functions in splicing and translation
title Autogenous cross-regulation of Quaking mRNA processing and translation balances Quaking functions in splicing and translation
title_full Autogenous cross-regulation of Quaking mRNA processing and translation balances Quaking functions in splicing and translation
title_fullStr Autogenous cross-regulation of Quaking mRNA processing and translation balances Quaking functions in splicing and translation
title_full_unstemmed Autogenous cross-regulation of Quaking mRNA processing and translation balances Quaking functions in splicing and translation
title_short Autogenous cross-regulation of Quaking mRNA processing and translation balances Quaking functions in splicing and translation
title_sort autogenous cross-regulation of quaking mrna processing and translation balances quaking functions in splicing and translation
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5695090/
https://www.ncbi.nlm.nih.gov/pubmed/29021242
http://dx.doi.org/10.1101/gad.302059.117
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