一个PtdIns4,5P2-调节的核聚合酶控制了选择的mRNAs的表达
David L Mellman1, Michael L Gonzales, Chunhua Song
1Program in Molecular and Cellular Pharmacology, University of Wisconsin Medical School, University of Wisconsin-Madison, 1300 University Avenue, Madison, Wisconsin 53706, USA.
Nature
|February 22, 2008
概括
核酸氨酸-4,5-双酸盐 (PtdIns4,5P2) 通过与Star-PAP相互作用来调节基因表达. 这种脂质信号分子控制mRNA3'-end的形成,影响氧化应激反应基因.
科学领域:
- 分子生物学分子生物学
- 细胞信号传输 细胞信号传输
- 基因表达规范 基因表达规范
背景情况:
- 酸是关键的脂质信号分子,调节真核细胞细胞功能.
- 酸丁醇-4,5-双酸盐 (PtdIns4,5P2) 是酸信号传递的核心,由I型酸丁醇4-酸5-激酶 (PIPKI) 生成.
- 虽然氨酸在核中起作用,但它们的直接调节机制仍然不清楚.
研究的目的:
- 阐明核PtdIns4,5P2在调节核功能中的作用.
- 为了确定与核PIPK相互作用的蛋白质伙伴,PIPKIalpha.
主要方法:
- 共同定位研究以确定核内的PIPKIalpha定位.
- 蛋白与蛋白相互作用测试以确定PIPKIalpha. 的结合伙伴.
- 生物化学试验,以评估PtdIns4,5P2对Star-PAP活动的调节作用.
- 对由PIPKIalpha-Star-PAP复合体调节的特定基因的mRNA3'-end形成的分析.
主要成果:
- 皮普基阿尔法与一种名为Star-PAP的新型非正规聚A聚合酶共同定位在核斑点上.
- 星星PAP活动受到PtdIns4,5P2.2的特别监管.
- 该PIPKIalpha-Star-PAP复合体通过调节mRNA3'-end形成来控制选择的mRNAs的表达,包括用于血氧酶-1和其他氧化应激反应基因的mRNAs.
结论:
- 一种新的机制揭示了核类酸信号与基因表达调节的整合.
- PIPKIalpha和Star-PAP形成了一个复合体,通过3'-end处理调节mRNA生物合成.
- 这一途径突显了细胞核中的脂质信号如何控制关键基因的表达,例如那些参与氧化应激反应的基因.
相关概念视频
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...
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Regulated mRNA Transport
In eukaryotes, transcription and translation are compartmentalized; an mRNA is first synthesized in the nucleus and then selectively transported to the cytoplasm for protein synthesis. Before transport, a pre-mRNA undergoes several steps of post-transcriptional modifications including splicing, 5' capping, and the addition of a poly-adenine tail. Various proteins bind to the pre-mRNA during these modifications. The mRNA transport takes place with the help of multiple proteins playing specific...
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...
Regulated mRNA Transport
In eukaryotes, transcription and translation are compartmentalized; an mRNA is first synthesized in the nucleus and then selectively transported to the cytoplasm for protein synthesis. Before transport, a pre-mRNA undergoes several steps of post-transcriptional modifications including splicing, 5' capping, and the addition of a poly-adenine tail. Various proteins bind to the pre-mRNA during these modifications. The mRNA transport takes place with the help of multiple proteins playing specific...
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...


