通过FMRP在发育中的大脑皮层中对NOS1进行物种依赖的转录后调节
Kenneth Y Kwan1, Mandy M S Lam, Matthew B Johnson
1Department of Neurobiology and Kavli Institute for Neuroscience, Yale University School of Medicine, New Haven, CT 06510, USA.
Cell
|May 15, 2012
概括
脆弱X综合征 (FXS) 涉及FMRP蛋白质的损失,影响智力障碍. 这项研究揭示了FMRP调节人类发育中的大脑中的NOS1蛋白转化,这对认知功能至关重要.
科学领域:
- 神经科学是一个神经科学.
- 发展生物学 发展生物学
- 遗传学 是一个遗传学.
背景情况:
- 脆弱X综合征 (FXS) 是智力障碍和自闭症的主要遗传原因.
- 它源于脆弱X智力障碍蛋白 (FMRP) 的功能丧失.
研究的目的:
- 调查FMRP在调节神经元氧化合成酶1 (NOS1) 在人类新皮质发育中的翻译中的作用.
- 了解FMRP对NOS1的调节如何为FXS病理生理学作出贡献.
主要方法:
- 检查了人类新皮层神经元发育中的FMRP和NOS1共同表达模式.
- 研究了FMRP介导NOS1翻译的机制,包括绑定动机.
- 在人类的FXS病例和缺乏FMRP的小鼠中比较NOS1蛋白水平.
主要成果:
- FMRP调节了NOS1mRNA在人类新皮质金字塔神经元发育中的翻译.
- 人类NOS1的翻译通过特定的编码区域动机被FMRP激活.
- 在发育中的人类FXS新皮质中,NOS1蛋白水平显著降低,但在缺乏FMRP的小鼠中并非如此.
结论:
- FMRP对NOS1的转录后调节对于新皮层电路的发展至关重要.
- FMRP介导的NOS1转化失调可能是脆弱X综合征认知缺陷的基础.
相关概念视频
Regulation of Expression at Multiple Steps
The gene expression in cells is regulated at different stages: (i) transcription, (ii) RNA processing, (iii) RNA localization, and (iv) translation. Transcriptional regulation is mediated by regulatory proteins such as transcription factors, activators, or repressors—these control gene expression by initiating or inhibiting the transcription of genes. Once a precursor or pre-mRNA is produced, it undergoes post-transcriptional modification, including 5' capping, splicing, and the addition of a...
Transcriptional Regulation: Riboswitches
Riboswitches are RNA elements that regulate gene expression by altering their secondary structures in response to specific effector molecules. These elements, located in the leader regions of certain mRNAs, act as transcriptional regulators by toggling between alternative conformations to control downstream gene expression. Riboswitch-mediated regulation is a precise mechanism for modulating biosynthetic pathways, as exemplified by the riboflavin biosynthesis pathway in Bacillus...
Regulation of Nuclear Protein Sorting
Nuclear protein sorting regulates nucleus composition and gene expression, crucial for determining the fate of a eukaryotic cell. Hence, the entry and exit of molecules across the nuclear envelope is a tightly controlled process. Nuclear protein sorting can be inhibited by one of the following ways: 1) masking cargo signal sequences, 2) modifying the nuclear receptor's affinity for cargo, 3) controlling the nuclear pore size, 4) retaining the cargo during its transit to the cytosol or the...
Chromatin Structure Regulates pre-mRNA Processing
In eukaryotic cells, nascent mRNA transcripts need to undergo many post-transcriptional modifications to reach the cell cytoplasm and translate into functional proteins. For a long time, transcription and pre-mRNA processing were considered two independent events that occur sequentially in the cell. However, it has now been well established that transcription and pre-mRNA processing are two simultaneous processes that are precisely regulated inside the cell.
The chromatin structure, especially...
The chromatin structure, especially...
Regulation of Expression Occurs at Multiple Steps
Gene expression can be regulated at almost every step from gene to protein. Transcription is the step that is most commonly regulated. This involves the binding of proteins to short regulatory sequences on the DNA. This association can either promote or inhibit the transcription of a gene associated with the respective sequence.
Transcription results in the generation of precursor (pre-mRNA) that consists of both exons and introns, which needs further processing before being translated to a...
Transcription results in the generation of precursor (pre-mRNA) that consists of both exons and introns, which needs further processing before being translated to a...
Regulation of Expression Occurs at Multiple Steps
Gene expression can be regulated at almost every step from gene to protein. Transcription is the step that is most commonly regulated. This involves the binding of proteins to short regulatory sequences on the DNA. This association can either promote or inhibit the transcription of a gene associated with the respective sequence.
Transcription results in the generation of precursor (pre-mRNA) that consists of both exons and introns, which needs further processing before being translated to a...
Transcription results in the generation of precursor (pre-mRNA) that consists of both exons and introns, which needs further processing before being translated to a...


