NMD abnormalities during brain development in the Fmr1-knockout mouse model of fragile X syndrome

Abstract Background Fragile X syndrome (FXS) is an intellectual disability attributable to loss of fragile X protein (FMRP). We previously demonstrated that FMRP binds mRNAs targeted for nonsense-mediated mRNA decay (NMD) and that FMRP loss results in hyperactivated NMD and inhibition of neuronal di...

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Autores principales:	Tatsuaki Kurosaki, Hitomi Sakano, Christoph Pröschel, Jason Wheeler, Alexander Hewko, Lynne E. Maquat
Formato:	article
Lenguaje:	EN
Publicado:	BMC 2021
Materias:	Nonsense-mediated mRNA decay (NMD) Fragile X protein (FMRP), Upframeshift protein 1 (UPF1) Fmr1-KO mouse Mouse brain development Cortex Hippocampus Biology (General) QH301-705.5 Genetics QH426-470
Acceso en línea:	https://doaj.org/article/a0a799aab3524b98be9f5f34a7a8b37c
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spelling	oai:doaj.org-article:a0a799aab3524b98be9f5f34a7a8b37c2021-11-21T12:41:56ZNMD abnormalities during brain development in the Fmr1-knockout mouse model of fragile X syndrome10.1186/s13059-021-02530-91474-760Xhttps://doaj.org/article/a0a799aab3524b98be9f5f34a7a8b37c2021-11-01T00:00:00Zhttps://doi.org/10.1186/s13059-021-02530-9https://doaj.org/toc/1474-760XAbstract Background Fragile X syndrome (FXS) is an intellectual disability attributable to loss of fragile X protein (FMRP). We previously demonstrated that FMRP binds mRNAs targeted for nonsense-mediated mRNA decay (NMD) and that FMRP loss results in hyperactivated NMD and inhibition of neuronal differentiation in human stem cells. Results We show here that NMD is hyperactivated during the development of the cerebral cortex, hippocampus, and cerebellum in the Fmr1-knockout (KO) mouse during embryonic and early postnatal periods. Our findings demonstrate that NMD regulates many neuronal mRNAs that are important for mouse brain development. Conclusions We reveal the abnormal regulation of these mRNAs in the Fmr1-KO mouse, a model of FXS, and highlight the importance of early intervention.Tatsuaki KurosakiHitomi SakanoChristoph PröschelJason WheelerAlexander HewkoLynne E. MaquatBMCarticleNonsense-mediated mRNA decay (NMD)Fragile X protein (FMRP), Upframeshift protein 1 (UPF1)Fmr1-KO mouseMouse brain developmentCortexHippocampusBiology (General)QH301-705.5GeneticsQH426-470ENGenome Biology, Vol 22, Iss 1, Pp 1-13 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Nonsense-mediated mRNA decay (NMD) Fragile X protein (FMRP), Upframeshift protein 1 (UPF1) Fmr1-KO mouse Mouse brain development Cortex Hippocampus Biology (General) QH301-705.5 Genetics QH426-470
spellingShingle	Nonsense-mediated mRNA decay (NMD) Fragile X protein (FMRP), Upframeshift protein 1 (UPF1) Fmr1-KO mouse Mouse brain development Cortex Hippocampus Biology (General) QH301-705.5 Genetics QH426-470 Tatsuaki Kurosaki Hitomi Sakano Christoph Pröschel Jason Wheeler Alexander Hewko Lynne E. Maquat NMD abnormalities during brain development in the Fmr1-knockout mouse model of fragile X syndrome
description	Abstract Background Fragile X syndrome (FXS) is an intellectual disability attributable to loss of fragile X protein (FMRP). We previously demonstrated that FMRP binds mRNAs targeted for nonsense-mediated mRNA decay (NMD) and that FMRP loss results in hyperactivated NMD and inhibition of neuronal differentiation in human stem cells. Results We show here that NMD is hyperactivated during the development of the cerebral cortex, hippocampus, and cerebellum in the Fmr1-knockout (KO) mouse during embryonic and early postnatal periods. Our findings demonstrate that NMD regulates many neuronal mRNAs that are important for mouse brain development. Conclusions We reveal the abnormal regulation of these mRNAs in the Fmr1-KO mouse, a model of FXS, and highlight the importance of early intervention.
format	article
author	Tatsuaki Kurosaki Hitomi Sakano Christoph Pröschel Jason Wheeler Alexander Hewko Lynne E. Maquat
author_facet	Tatsuaki Kurosaki Hitomi Sakano Christoph Pröschel Jason Wheeler Alexander Hewko Lynne E. Maquat
author_sort	Tatsuaki Kurosaki
title	NMD abnormalities during brain development in the Fmr1-knockout mouse model of fragile X syndrome
title_short	NMD abnormalities during brain development in the Fmr1-knockout mouse model of fragile X syndrome
title_full	NMD abnormalities during brain development in the Fmr1-knockout mouse model of fragile X syndrome
title_fullStr	NMD abnormalities during brain development in the Fmr1-knockout mouse model of fragile X syndrome
title_full_unstemmed	NMD abnormalities during brain development in the Fmr1-knockout mouse model of fragile X syndrome
title_sort	nmd abnormalities during brain development in the fmr1-knockout mouse model of fragile x syndrome
publisher	BMC
publishDate	2021
url	https://doaj.org/article/a0a799aab3524b98be9f5f34a7a8b37c
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NMD abnormalities during brain development in the Fmr1-knockout mouse model of fragile X syndrome

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