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Abstract：
Fragile X syndrome (FXS) is caused by the loss of fragile X mental retardation protein (FMRP), an RNA binding protein whose deficiency impacts many brain functions, including differentiation of adult neural stem cells (aNSCs). However, the mechanism by which FMRP influences these processes remains unclear. Here, we performed ribosome profiling and transcriptomic analysis of aNSCs in parallel from wild-type and Fmr1 knockout mice. Our data revealed diverse gene expression changes at both mRNA and translation levels. Many mitosis and neurogenesis genes were dysregulated primarily at the mRNA level, while numerous synaptic genes were mostly dysregulated at the translation level. Translational \"buffering\", whereby changes in ribosome association with mRNA are compensated by alterations in RNA abundance, was also evident. Knockdown of NECDIN, an FMRP-repressed transcriptional factor, rescued neuronal differentiation. In addition, we discovered that FMRP regulates mitochondrial mRNA expression and energy homeostasis. Thus, FMRP controls diverse transcriptional and posttranscriptional gene expression programs critical for neural differentiation.
摘要：
脆性X综合征（FXS）是由脆性X智力低下蛋白（FMRP）的缺失引起的，一种RNA结合蛋白，其缺陷会影响许多大脑功能，包括成人神经干细胞（aNSC）的分化。然而,FMRP影响这些过程的机制尚不清楚.这里,我们对野生型和Fmr1基因敲除小鼠的aNSCs进行了核糖体分析和转录组分析.我们的数据揭示了mRNA和翻译水平的不同基因表达变化。许多有丝分裂和神经发生基因主要在mRNA水平失调，而许多突触基因大多在翻译水平失调。翻译\"缓冲\",通过RNA丰度的改变来补偿核糖体与mRNA结合的变化，也很明显。击倒NECDIN,FMRP抑制的转录因子，拯救神经元分化。此外,我们发现FMRP调节线粒体mRNA表达和能量稳态。因此，FMRP控制对神经分化至关重要的多种转录和转录后基因表达程序。
