转化暂停确保了XBP1umRNA的膜向和细胞质剪接
Kota Yanagitani1, Yukio Kimata, Hiroshi Kadokura
1Laboratory of Molecular and Cell Genetics, Graduate School of Biological Sciences, Nara Institute of Science and Technology, 8916-5, Takayama, Ikoma, Nara 630-0192, Japan.
概括
细胞内膜网膜 (ER) 的压力触发了X-box-binding protein 1 mRNA (XBP1u mRNA) 的剪接,由需要伊诺西的酶-1α. 翻译性暂停XBP1umRNA稳定了复杂的高效拼接.
科学领域:
- 分子生物学分子生物学
- 细胞应激反应的应激反应
- 基因表达规范 基因表达规范
背景情况:
- 细胞内膜网膜 (ER) 的压力激活了需要内醇的酶-1α (IRE1α),一种内核酶.
- IRE1α将X盒结合蛋白1mRNA (XBP1u mRNA) 拼接在一起,产生一个活性转录因子 (XBP1s),减轻ER压力.
研究的目的:
- 研究XBP1umRNA针对ER膜进行拼接的机制.
- 确定新生在mRNA-ribosome-nascent chain (R-RNC) 复杂局部化和拼接效率中的作用.
主要方法:
- 使用XBP1u的突变分析.
- 在翻译过程中研究了mRNA-ribosome-nascent chain (R-RNC) 综合体的动态.
- 研究了特定模块在翻译调节和mRNA向中的作用.
主要成果:
- 发现XBP1umRNA的翻译暂时暂停.
- 在XBP1u中确定了一种进化保守的C端模块,该模块负责转化暂停.
- 证明这种模块对于高效的R-RNC复合体稳定,ER膜向和随后的拼接至关重要.
结论:
- XBP1u mRNA的转化暂停是稳定ER膜R-RNC复合物的关键机制.
- 保存的C端模块在调节翻译和促进高效的XBP1mRNA拼接方面发挥着至关重要的作用.
- 翻译性暂停是一种多功能机制,用于哺乳动物细胞内的各种细胞过程.
相关概念视频
Post-translational Translocation of Proteins to the RER
A sizable fraction of proteins destined for ER are first synthesized in the cell cytosol and then transported across the ER membrane–a process called post-translational translocation. Similar to cotranslationally translocated proteins, these proteins also use the Sec translocon complex to enter the ER lumen.
Targeting proteins to the ER
Hsp40 and Hsp70 chaperone molecules bind the translated proteins in the cytosol to prevent their folding. The chaperone binding helps to keep the signal...
Targeting proteins to the ER
Hsp40 and Hsp70 chaperone molecules bind the translated proteins in the cytosol to prevent their folding. The chaperone binding helps to keep the signal...
Cotranslational Protein Translocation
Translocation of proteins across membranes is an ancient process that occurs even in bacteria and archaebacteria. In fact, the components of the translocation machinery are still conserved between prokaryotes and eukaryotes.
Sec61 channel partners for cotranslational translocation
During cotranslational translocation, the Sec61 channel partners with the signal recognition particle (SRP), the signal recognition particle receptor (SR), and the ribosomes to transport the nascent polypeptide chain...
Sec61 channel partners for cotranslational translocation
During cotranslational translocation, the Sec61 channel partners with the signal recognition particle (SRP), the signal recognition particle receptor (SR), and the ribosomes to transport the nascent polypeptide chain...
Nonsense-mediated mRNA Decay
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,...
Directing Proteins to the Rough Endoplasmic Reticulum
The organelle-specific signaling sequences direct proteins synthesized in the cytosol to their final destination like ER, mitochondria, peroxisomes, etc. Some of the proteins directed to ER are then trafficked via vesicles to other organelles within the cell or the extracellular environment through the Golgi complex. For example, the rough ER synthesizes soluble proteins for transportation to the lysosomes or secretion out of the cell. It can also synthesize transmembrane proteins that can...
RNA Splicing
Splicing is the process by which eukaryotic RNA is edited before its translation into protein. The RNA strand transcribed from eukaryotic DNA is called the primary transcript. The primary transcripts that become mRNAs are called precursor messenger RNAs (pre-mRNAs). Eukaryotic pre-mRNA contains alternating sequences of exons and introns. Exons are nucleotide sequences that code for proteins, whereas introns are the non-coding regions. In RNA splicing, introns are removed and exons are bonded...
RNA Splicing
Splicing is the process by which eukaryotic RNA is edited before its translation into protein. The RNA strand transcribed from eukaryotic DNA is called the primary transcript. The primary transcripts that become mRNAs are called precursor messenger RNAs (pre-mRNAs). Eukaryotic pre-mRNA contains alternating sequences of exons and introns. Exons are nucleotide sequences that code for proteins, whereas introns are the non-coding regions. In RNA splicing, introns are removed and exons are bonded...


