التفاصيل البيبلوغرافية
| العنوان: |
Species-specific FMRP regulation of RACK1 is critical for prenatal cortical development. |
| المؤلفون: |
Shen, Minjie1,2 (AUTHOR), Sirois, Carissa L.1,2 (AUTHOR), Guo, Yu1,2 (AUTHOR), Li, Meng1,2 (AUTHOR), Dong, Qiping1 (AUTHOR), Méndez-Albelo, Natasha M.1,2,3 (AUTHOR), Gao, Yu1,2 (AUTHOR), Khullar, Saniya1,4 (AUTHOR), Kissel, Lee5 (AUTHOR), Sandoval, Soraya O.1,2,5 (AUTHOR), Wolkoff, Natalie E.1,2 (AUTHOR), Huang, Sabrina X.1,2 (AUTHOR), Xu, Zhiyan1,2,6 (AUTHOR), Bryan, Jonathan E.1,4 (AUTHOR), Contractor, Amaya M.1,2 (AUTHOR), Korabelnikov, Tomer1,2 (AUTHOR), Glass, Ian A.7 (AUTHOR), Doherty, Dan7 (AUTHOR), Levine, Jon E.2,8 (AUTHOR), Sousa, André M.M.1,2 (AUTHOR) |
| المصدر: |
Neuron. Dec2023, Vol. 111 Issue 24, p3988-3988. 1p. |
| مصطلحات موضوعية: |
*FETAL development, *FRAGILE X syndrome, *AUTISM spectrum disorders, *NEURAL development, *FETAL brain |
| مستخلص: |
Fragile X messenger ribonucleoprotein 1 protein (FMRP) deficiency leads to fragile X syndrome (FXS), an autism spectrum disorder. The role of FMRP in prenatal human brain development remains unclear. Here, we show that FMRP is important for human and macaque prenatal brain development. Both FMRP-deficient neurons in human fetal cortical slices and FXS patient stem cell-derived neurons exhibit mitochondrial dysfunctions and hyperexcitability. Using multiomics analyses, we have identified both FMRP-bound mRNAs and FMRP-interacting proteins in human neurons and unveiled a previously unknown role of FMRP in regulating essential genes during human prenatal development. We demonstrate that FMRP interaction with CNOT1 maintains the levels of receptor for activated C kinase 1 (RACK1), a species-specific FMRP target. Genetic reduction of RACK1 leads to both mitochondrial dysfunctions and hyperexcitability, resembling FXS neurons. Finally, enhancing mitochondrial functions rescues deficits of FMRP-deficient cortical neurons during prenatal development, demonstrating targeting mitochondrial dysfunction as a potential treatment. [Display omitted] • FMRP is critical for mitochondrial functions in developing human cortical neurons • FMRP interacts with and regulates essential genes during human prenatal development • FMRP interacts with CNOT1 to regulate RACK1, a species-specific FMRP target • Enhancing mitochondrial functions rescues hyperexcitability of FXS neurons Shen et al. demonstrate that FMRP is critical for prenatal human brain development through regulating mitochondrial functions. They have discovered that FMRP interacts with other proteins to regulate genes important for neuronal development. They show that enhancing mitochondrial functions rescues the hyperexcitability of human fragile X syndrome patient-derived neurons. [ABSTRACT FROM AUTHOR] |
| قاعدة البيانات: |
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