Cytoplasmic Polyadenylation Element-Binding Protein 1 Post-transcriptionally Regulates Fragile X Mental Retardation 1 Expression Through 3′ Untranslated Region in Central Nervous System Neurons

Oe, Souichi; Hayashi, S.; Tanaka, Susumu; Koike, Taro; Hirahara, Yukie; Seki-Omura, Ryohei; Kakizaki, Rio; Sakamoto, Sumika; Nakano, Yosuke; Noda, Yasuko; Yamada, Hisao; Kitada, Masaaki

doi:10.3389/fncel.2022.869398

Cited by 3 publications

(1 citation statement)

References 60 publications

(66 reference statements)

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“…The CPEB1 protein is known to be critical for oogenesis and oocyte maturation in flies, zebrafish and mice (Bally-Cuif et al, 1998;Christerson and Mckearin, 1994;Hake and Richter, 1994;O'Connell et al, 2014;Takahashi et al, 2023). A functional interaction between FMRP and CPEB1 is also well reported in multiple contexts, where both proteins regulate each other's activities, predominantly in an antagonistic fashion (Oe et al, 2022;Shin et al, 2022). The strongest evidence we see of the FMRP-Zorba functional interaction in our model is in late stage oocytes from older females, where both in the KO and in wildtype oocytes injected with an FMRP antibody, there is a reduction of zorba mRNA and protein levels, as well as altered polyA profiles of known Zorba targets (in the KO).…”

Section: Discussionmentioning

confidence: 99%

Impaired ovarian development in a zebrafishfmr1knockout model

Rani,

Sri,

Medishetti

et al. 2024

Preprint

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Fragile X syndrome (FXS) is an inherited neurodevelopmental disorder and the leading genetic cause of autism spectrum disorders. FXS is caused by loss of function mutations in Fragile X mental retardation protein (FMRP), an RNA binding protein that is known to regulate translation of its target mRNAs, predominantly in the brain and gonads. The molecular mechanisms connecting FMRP function to neurodevelopmental phenotypes are well understood. However, neither the full extent of reproductive phenotypes, nor the underlying molecular mechanisms have been as yet determined. Here, we developed newfmr1knockout zebrafish lines and show that they mimic key aspects of FXS neuronal phenotypes across both larval and adult stages. Results from thefmr1knockout females also showed that altered gene expression in the brain, via the neuroendocrine pathway contribute to distinct abnormal phenotypes during ovarian development and oocyte maturation. We identified at least three mechanisms underpinning these defects, including altered neuroendocrine signaling in sexually mature females resulting in accelerated ovarian development, altered expression of germ cell and meiosis promoting genes at various stages during oocyte maturation, and finally a strong mitochondrial impairment in late stage oocytes from knockout females. Our findings have implications beyond FXS in the study of reproductive function and female infertility. Dissection of the translation control pathways during ovarian development using models like the knockout lines reported here may reveal novel approaches and targets for fertility treatments.Abstract FigureGraphical Abstract

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Section: Discussionmentioning

confidence: 99%

Impaired ovarian development in a zebrafishfmr1knockout model

Rani,

Sri,

Medishetti

et al. 2024

Preprint

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Loss of FMRP affects ovarian development and behaviour through multiple pathways in a zebrafish model of fragile X syndrome

Rani,

Sri,

Medishetti

et al. 2024

Human Molecular Genetics

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Fragile X syndrome (FXS) is an inherited neurodevelopmental disorder and the leading genetic cause of autism spectrum disorders. FXS is caused by loss of function mutations in Fragile X mental retardation protein (FMRP), an RNA binding protein that is known to regulate translation of its target mRNAs, predominantly in the brain and gonads. The molecular mechanisms connecting FMRP function to neurodevelopmental phenotypes are well understood. However, neither the full extent of reproductive phenotypes, nor the underlying molecular mechanisms have been as yet determined. Here, we developed new fmr1 knockout zebrafish lines and show that they mimic key aspects of FXS neuronal phenotypes across both larval and adult stages. Results from the fmr1 knockout females also showed that altered gene expression in the brain, via the neuroendocrine pathway contribute to distinct abnormal phenotypes during ovarian development and oocyte maturation. We identified at least three mechanisms underpinning these defects, including altered neuroendocrine signaling in sexually mature females resulting in accelerated ovarian development, altered expression of germ cell and meiosis promoting genes at various stages during oocyte maturation, and finally a strong mitochondrial impairment in late stage oocytes from knockout females. Our findings have implications beyond FXS in the study of reproductive function and female infertility. Dissection of the translation control pathways during ovarian development using models like the knockout lines reported here may reveal novel approaches and targets for fertility treatments.

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Cytoplasmic Polyadenylation Element Binding Protein 1 and Atherosclerosis: Prospective Target and New Insights

Zhou,

Tang

2024

CVP

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The ribonucleic acid (RNA)-binding protein Cytoplasmic Polyadenylation Element Binding Protein 1 (CPEB1), a key member of the CPEB family, is essential in controlling gene expression involved in both healthy physiological and pathological processes. CPEB1 can bind to the 3'- untranslated regions (UTR) of substrate messenger ribonucleic acid (mRNA) and regulate its translation. There is increasing evidence that CPEB1 is closely related to the pathological basis of atherosclerosis. According to recent investigations, many pathological processes, including inflammation, lipid metabolism, endothelial dysfunction, angiogenesis, oxidative stress, cellular senescence, apoptosis, and insulin resistance, are regulated by CPEB1. This review considers the prevention and treatment of atherosclerotic heart disease in relation to the evolution of the physiological function of CPEB1, recent research breakthroughs, and the potential participation of CPEB1 in atherosclerosis.

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Cytoplasmic Polyadenylation Element-Binding Protein 1 Post-transcriptionally Regulates Fragile X Mental Retardation 1 Expression Through 3′ Untranslated Region in Central Nervous System Neurons

Cited by 3 publications

References 60 publications

Impaired ovarian development in a zebrafishfmr1knockout model

Impaired ovarian development in a zebrafishfmr1knockout model

Loss of FMRP affects ovarian development and behaviour through multiple pathways in a zebrafish model of fragile X syndrome

Cytoplasmic Polyadenylation Element Binding Protein 1 and Atherosclerosis: Prospective Target and New Insights

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