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The RNA-Binding Protein HuD Regulates Alternative Splicing and Alternative Polyadenylation in the Mouse Neocortex

The neuronal Hu/ELAV-like proteins HuB, HuC and HuD are a class of RNA-binding proteins that are crucial for proper development and maintenance of the nervous system. These proteins bind to AU-rich elements (AREs) in the untranslated regions (3′-UTRs) of target mRNAs regulating mRNA stability, trans...

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Autores principales: Sena, Rebecca M., Twiss, Jeffery L., Gardiner, Amy S., Dell’Orco, Michela, Linsenbardt, David N., Perrone-Bizzozero, Nora I.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8151252/
https://www.ncbi.nlm.nih.gov/pubmed/34064652
http://dx.doi.org/10.3390/molecules26102836
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author Sena, Rebecca M.
Twiss, Jeffery L.
Gardiner, Amy S.
Dell’Orco, Michela
Linsenbardt, David N.
Perrone-Bizzozero, Nora I.
author_facet Sena, Rebecca M.
Twiss, Jeffery L.
Gardiner, Amy S.
Dell’Orco, Michela
Linsenbardt, David N.
Perrone-Bizzozero, Nora I.
author_sort Sena, Rebecca M.
collection PubMed
description The neuronal Hu/ELAV-like proteins HuB, HuC and HuD are a class of RNA-binding proteins that are crucial for proper development and maintenance of the nervous system. These proteins bind to AU-rich elements (AREs) in the untranslated regions (3′-UTRs) of target mRNAs regulating mRNA stability, transport and translation. In addition to these cytoplasmic functions, Hu proteins have been implicated in alternative splicing and alternative polyadenylation in the nucleus. The purpose of this study was to identify transcriptome-wide effects of HuD deletion on both of these nuclear events using RNA sequencing data obtained from the neocortex of Elavl4(–/–) (HuD KO) mice. HuD KO affected alternative splicing of 310 genes, including 17 validated HuD targets such as Cbx3, Cspp1, Snap25 and Gria2. In addition, deletion of HuD affected polyadenylation of 53 genes, with the majority of significantly altered mRNAs shifting towards usage of proximal polyadenylation signals (PAS), resulting in shorter 3′-UTRs. None of these genes overlapped with those showing alternative splicing events. Overall, HuD KO had a greater effect on alternative splicing than polyadenylation, with many of the affected genes implicated in several neuronal functions and neuropsychiatric disorders.
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spelling pubmed-81512522021-05-27 The RNA-Binding Protein HuD Regulates Alternative Splicing and Alternative Polyadenylation in the Mouse Neocortex Sena, Rebecca M. Twiss, Jeffery L. Gardiner, Amy S. Dell’Orco, Michela Linsenbardt, David N. Perrone-Bizzozero, Nora I. Molecules Article The neuronal Hu/ELAV-like proteins HuB, HuC and HuD are a class of RNA-binding proteins that are crucial for proper development and maintenance of the nervous system. These proteins bind to AU-rich elements (AREs) in the untranslated regions (3′-UTRs) of target mRNAs regulating mRNA stability, transport and translation. In addition to these cytoplasmic functions, Hu proteins have been implicated in alternative splicing and alternative polyadenylation in the nucleus. The purpose of this study was to identify transcriptome-wide effects of HuD deletion on both of these nuclear events using RNA sequencing data obtained from the neocortex of Elavl4(–/–) (HuD KO) mice. HuD KO affected alternative splicing of 310 genes, including 17 validated HuD targets such as Cbx3, Cspp1, Snap25 and Gria2. In addition, deletion of HuD affected polyadenylation of 53 genes, with the majority of significantly altered mRNAs shifting towards usage of proximal polyadenylation signals (PAS), resulting in shorter 3′-UTRs. None of these genes overlapped with those showing alternative splicing events. Overall, HuD KO had a greater effect on alternative splicing than polyadenylation, with many of the affected genes implicated in several neuronal functions and neuropsychiatric disorders. MDPI 2021-05-11 /pmc/articles/PMC8151252/ /pubmed/34064652 http://dx.doi.org/10.3390/molecules26102836 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Sena, Rebecca M.
Twiss, Jeffery L.
Gardiner, Amy S.
Dell’Orco, Michela
Linsenbardt, David N.
Perrone-Bizzozero, Nora I.
The RNA-Binding Protein HuD Regulates Alternative Splicing and Alternative Polyadenylation in the Mouse Neocortex
title The RNA-Binding Protein HuD Regulates Alternative Splicing and Alternative Polyadenylation in the Mouse Neocortex
title_full The RNA-Binding Protein HuD Regulates Alternative Splicing and Alternative Polyadenylation in the Mouse Neocortex
title_fullStr The RNA-Binding Protein HuD Regulates Alternative Splicing and Alternative Polyadenylation in the Mouse Neocortex
title_full_unstemmed The RNA-Binding Protein HuD Regulates Alternative Splicing and Alternative Polyadenylation in the Mouse Neocortex
title_short The RNA-Binding Protein HuD Regulates Alternative Splicing and Alternative Polyadenylation in the Mouse Neocortex
title_sort rna-binding protein hud regulates alternative splicing and alternative polyadenylation in the mouse neocortex
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8151252/
https://www.ncbi.nlm.nih.gov/pubmed/34064652
http://dx.doi.org/10.3390/molecules26102836
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