YTHDF2以一种独立的方式通过UPF1促进了侵略性形成
Hyun Jung Hwang1, Tae Lim Park1, Hyeong-In Kim1
1Department of Biological Sciences, Korea Advanced Institute of Science and Technology, Daejeon, 34141, Republic of Korea.
Nature communications
|October 6, 2023
概括
YTHDF2蛋白在细胞蛋白质质量控制中发挥着至关重要的作用,它有助于通过独立于其已知的RNA结合功能而形成攻击性细胞. 它的缺失会损害错误折叠的蛋白质的运动,促进细胞死亡.
科学领域:
- 细胞生物学 细胞生物学
- 分子生物学分子生物学
- 生物化学 生物化学
背景情况:
- YTHDF2被称为一种RNA结合蛋白,其向N6甲基氨酸 (m6A) 修饰的RNA进行降解.
- 蛋白质稳态依赖于无素-蛋白酶体系统和侵略体的形成来隔离错误折叠的蛋白质.
研究的目的:
- 调查YTHDF2在侵略性形成中的作用,独立于其m6ARNA结合活性.
- 阐明YTHDF2影响错折聚的运动的机制.
主要方法:
- 在低调节YTHDF2表达的HeLa细胞中研究了YTHDF2功能.
- 分析了攻击体的形成,蛋白质聚合物的运动和细胞亡.
- 研究了涉及YTHDF2,UPF1和dynein的蛋白质-蛋白质相互作用.
主要成果:
- 降低YTHDF2的调节损害了攻击性细胞的形成,并降低了错误折叠的多的运动速度.
- YTHDF2与UPF1相互作用,形成一个复杂的错误折叠的多.
- YTHDF2增强了dynein运动蛋白的相互作用,促进了多的运输到侵略体.
- 降低YTHDF2水平促进了细胞亡.
结论:
- YTHDF2在蛋白质质量控制中具有关键的独立功能.
- YTHDF2通过与dynein运动复合体的相互作用,促进错误折叠的蛋白质的运输到侵略体.
- YTHDF2是侵略性细胞形成和细胞对蛋白质错折的反应的关键调节者.
相关概念视频
The Unfolded Protein Response
4.7K
The ER is the hub of protein synthesis in a cell. It has robust systems to quality control protein folding and also for degradation of terminally misfolded proteins. Under normal conditions, a small proportion of misfolded proteins that cannot be salvaged need to be transported to the cytoplasm by the ER-associated degradation or ERAD pathways. However, if the ERAD cannot handle the misfolded proteins, the cell activates the unfolded protein response or UPR to adjust the protein folding...
4.7K
Translocation of Proteins into the Mitochondria
3.1K
Mitochondrial precursors are translocated to the internal subcompartments via independent mechanisms involving distinct protein machineries called translocases.
Sorting of outer membrane proteins:
Mitochondrial outer membrane proteins are of two types: the transmembrane, beta-barrel porins, and the membrane-anchored, alpha-helical proteins. Beta-barrel porin precursors are translocated by the TOM complex and inserted into the outer mitochondrial membrane by the SAM complex. In contrast,...
Sorting of outer membrane proteins:
Mitochondrial outer membrane proteins are of two types: the transmembrane, beta-barrel porins, and the membrane-anchored, alpha-helical proteins. Beta-barrel porin precursors are translocated by the TOM complex and inserted into the outer mitochondrial membrane by the SAM complex. In contrast,...
3.1K
Nonsense-mediated mRNA Decay
10.7K
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,...
10.7K
Improving Translational Accuracy
11.4K
Base complementarity between the three base pairs of mRNA codon and the tRNA anticodon is not a failsafe mechanism. Inaccuracies can range from a single mismatch to no correct base pairing at all. The free energy difference between the correct and nearly correct base pairs can be as small as 3 kcal/ mol. With complementarity being the only proofreading step, the estimated error frequency would be one wrong amino acid in every 100 amino acids incorporated. However, error frequencies observed in...
11.4K
Disassembly of Intermediate Filaments
2.1K
Intermediate filaments (IFs) do not undergo spontaneous disassembly. Enzymes, kinases, and phosphatases add and remove phosphates from specific sites to regulate their disassembly. The IF concentration in the cytoplasm also regulates the disassembly. If the concentration crosses a threshold, it activates the protein kinases in the vicinity, allowing the phosphorylation of IFs.
Keratin proteins, found at the cell periphery near cell junctions, undergo a cycle of assembly and disassembly. In Type...
Keratin proteins, found at the cell periphery near cell junctions, undergo a cycle of assembly and disassembly. In Type...
2.1K
Transfer RNA Synthesis
12.0K
One of the unique features of tRNA is the presence of modified bases. In some tRNAs, modified bases account for nearly 20% of the total bases in the molecule. Altogether, these unusual bases protect the tRNA from enzymatic degradation by RNases.
Each of these chemical modifications is carried by a specific enzyme, post-transcription. All of these enzymes have unique base and site-specificity. Methylation, the most common chemical modification, is carried by at least nine different enzymes, with...
Each of these chemical modifications is carried by a specific enzyme, post-transcription. All of these enzymes have unique base and site-specificity. Methylation, the most common chemical modification, is carried by at least nine different enzymes, with...
12.0K


