主能量稳态调节器PGC-1α表现出mRNA核出口功能
Simeon R Mihaylov1,2, Lydia M Castelli1, Ya-Hui Lin1
1Sheffield Institute for Translational Neuroscience (SITraN), Department of Neuroscience, University of Sheffield, 385 Glossop Road, Sheffield, S10 2HQ, UK.
Nature communications
|September 7, 2023
概括
过氧体增殖器激活受体马协活性剂1-α (PGC-1α) 通过结合RNA和促进特定mRNA的核出口来调节线粒体功能. 这揭示了能量代谢和衰老中的新角色.
科学领域:
- 分子生物学分子生物学
- 细胞的新陈代谢
- 基因规则 基因规则
背景情况:
- PGC-1α是线粒体生物发生和能量恒温的关键调节者.
- 它的RNA处理功能,特别是涉及RS域,仍然在很大程度上未被探索.
- 了解PGC-1α的非转录作用对于代谢和与年龄相关的疾病研究至关重要.
研究的目的:
- 为了研究PGC-1α RS域的RNA结合和核出口功能.
- 通过其RNA相互作用调节的新型PGC-1α点和途径的识别.
- 阐明PGC-1α在维护线粒体平衡中的作用.
主要方法:
- 同免疫沉测试检测RNA和NXF1结合.
- 可诱导的PGC-1α衰减和RS删除突变的表达.
- RNA测序和全基因组分析.
- 对mRNA核出口和线粒体基因表达的分析.
主要成果:
- 该PGC-1α RS域直接结合RNA和核出口受体NXF1.1.
- PGC-1α的RNA/NXF1结合活性对于特定线粒体mRNA和线粒体平衡的核出口至关重要.
- 全基因组研究表明,PGC-1α调节了基因在非同源端结合和核细胞质运输中的基因,独立于促进体结合.
结论:
- PGC-1α具有由其RS域介导的关键RNA输出功能.
- 这一功能对线粒体平衡至关重要,并将PGC-1α与超越转录协同激活的更广泛的细胞过程联系起来.
- 这些发现为了解PGC-1α在代谢障碍,衰老和神经退行方面的作用开辟了新的途径.
相关概念视频
Nuclear Export
3.7K
The nucleus restricts several proteins within and allows others to pass. The restricted proteins possess a nuclear retention sequence or NRS, anchoring them to the nuclear lamins and preventing their transport to the cytosol. The non-restricted proteins, after their synthesis, are transported to their site of action, such as the cytosol or other organelles, with the help of nuclear export signals or NES.
NES are of three types- the canonical 10-residue long leucine-rich signal and other...
NES are of three types- the canonical 10-residue long leucine-rich signal and other...
3.7K
Nuclear Export of mRNA
7.7K
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...
7.7K
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
Nuclear Protein Sorting
4.7K
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...
4.7K
Directionality of Nuclear Transport
3.3K
Ras-related nuclear protein or Ran is a small G protein that cycles between its GTP and GDP bound states. Ran specific regulators, a Ran GTPase Activating Protein or RanGAP present in the cytosol and a Ran guanine nucleotide exchange factor or RanGEF present inside the nucleus regulate GTP/GDP exchange. A high concentration of GTP inside the cells, in addition to this asymmetric distribution of Ran-specific regulators, leads to a higher RanGTP concentration inside the nucleus. This...
3.3K
Regulated mRNA Transport
6.3K
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...
6.3K


