亚细胞mRNA动态建模揭示了核保留作为限制速度的核保留
David Steinbrecht1,2, Igor Minia3, Miha Milek4
1Charite-Universitätsmedizin Berlin, Institute of Pathology, Berlin, Germany.
Molecular systems biology
|November 15, 2024
概括
这项研究揭示了mRNA如何在小鼠干细胞中的细胞区之间移动. 核保留是大多数mRNA的一个关键瓶,而转录因子mRNA迅速移动,突出显示了模块化基因调节.
科学领域:
- 分子生物学分子生物学
- 细胞生物学 细胞生物学
- 系统生物学 系统生物学
背景情况:
- 细胞mRNA处理,翻译和降解发生在不同的亚细胞位置.
- 了解这些区间的mRNA动态对于基因表达调节至关重要.
研究的目的:
- 量化核,细胞和膜相关区间之间的mRNA流速和半衰期.
- 研究mRNA转录的动力学,包括转录因子和线粒体蛋白质的转录因子.
- 探索基因表达的时空调节.
主要方法:
- 代谢性RNA标签的标记
- 生物化学分化方法 生物化学分化方法
- 在mRNA测序过程中,
- 数学建模的数学建模
- 在小鼠胚胎干细胞中分析了9000多个基因.
主要成果:
- 核前mRNA,核成熟mRNA,细胞质mRNA和与膜相关的mRNA的确定半衰期.
- 确定核保留作为许多成熟mRNA的速度限制步骤.
- 观察到转录因子mRNAs的快速动力学和短核半衰期.
- 对差异局部化mRNAs展示了不同的速率常数组合,表明模块化调节.
- 在它们各自的区间中发现了膜局部化和细胞质mRNA的高稳定性.
- 表明核编码的线粒体蛋白质的转录表现出长时间的核保留,但细胞质动力学不反映共同翻译向.
结论:
- 亚细胞区间之间的mRNA流是严格调节的,核保留作为一个重要的控制点.
- 特定的mRNA群体,就像编码转录因子的群体一样,表现出不同的动力特征.
- 不同的mRNA定位是由模块化调节机制控制的.
- 这项研究为研究空间时间基因表达控制提供了全面的资源.
相关概念视频
Nuclear Export of mRNA
7.6K
Before mRNAs are exported to the cytoplasm, it is crucial to check each mRNA for structural and functional integrity. Eukaryotic cells use several different mechanisms, collectively known as mRNA surveillance, to look for irregularities in mRNAs. Irregular or aberrant mRNA are rapidly degraded by various enzymes. If a defective mRNA escapes the surveillance, it would be translated into a protein which would either be non-functional or not function properly. One of the primary irregularities in...
7.6K
Regulated mRNA Transport
6.2K
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...
6.2K
Regulation of Nuclear Protein Sorting
2.4K
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...
2.4K
Chromatin Structure Regulates pre-mRNA Processing
6.9K
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...
6.9K
Nuclear Protein Sorting
4.6K
Nuclear protein sorting is the selective trafficking of histones, polymerases, gene regulatory proteins into the nucleus and exporting RNAs and ribosomes to the cytosol. It is a tightly controlled process that regulates gene expression within a cell.
Proteins targeted to the nucleus carry nuclear localization signals or NLS recognized by import receptors in the cytosol. Similarly, proteins with nuclear export signals are recognized by export receptors. Import and export receptors are...
Proteins targeted to the nucleus carry nuclear localization signals or NLS recognized by import receptors in the cytosol. Similarly, proteins with nuclear export signals are recognized by export receptors. Import and export receptors are...
4.6K
Nonsense-mediated mRNA Decay
10.6K
The Upf proteins that carry out nonsense-mediated decay (NMD) are found in all eukaryotic organisms, including humans. Each protein has an individual role, but they need to work in collaboration. Upf1 is an ATP-dependent RNA helicase that unwinds the RNA helix. Because Upf1 can unwind any RNA, Upf2 and Upf3 are required to help Upf1 discriminate between nonsense and normal mRNAs.
Usually, Upf3 binds to an Exon Junction Complex (EJC) at mRNA splice sites. If a ribosome fully translates the mRNA,...
Usually, Upf3 binds to an Exon Junction Complex (EJC) at mRNA splice sites. If a ribosome fully translates the mRNA,...
10.6K


