对于在未折叠的蛋白质反应中进行调节的mRNA剪接,需要tRNA结合酶
C Sidrauski1, J S Cox, P Walter
1Department of Biochemistry and Biophysics, University of California School of Medicine, San Francisco 94143-0448, USA.
Cell
|November 1, 1996
概括
在tRNA结合酶中发生的突变会通过阻断HAC1mRNA的拼接来破坏酵母中展开的蛋白质反应 (UPR). 这表明HAC1mRNA处理的新型,spliceosome独立的途径.
科学领域:
- 分子生物学分子生物学
- 细胞生物学 细胞生物学
- 酵母遗传学 酵母遗传学
背景情况:
- 展开的蛋白质反应 (UPR) 是一个关键的细胞通路,由内质网膜 (ER) 应激激活.
- UPR的激活涉及转录因子Hac1p,其活性由mRNA拼接调节.
- 了解UPR调节对于理解细胞应激反应至关重要.
研究的目的:
- 研究调节Hac1p活动的分子机制.
- 为了确定参与HAC1mRNA的特定拼接的因素.
- 阐明控制Saccharomyces cerevisiae中展开的蛋白质反应的途径.
主要方法:
- 基因查以确定影响UPR的突变.
- 在突变酵母菌株中对HAC1mRNA拼接的分析.
- 对HAC1mRNA拼接与正规拼接酶体介导拼接的比较.
- 在HAC1 mRNA中拼接连接序列的表征.
主要成果:
- 发现tRNA结合酶的突变专门阻止了HAC1mRNA拼接,破坏了UPR.
- HAC1 mRNA拼接在缺乏拼接酶介导拼接的酵母突变体中没有受到影响.
- HAC1mRNA的拼接接口偏离了其他酵母前mRNA中发现的共识序列.
- 这些发现表明HAC1mRNA的新拼接途径.
结论:
- 调节HAC1mRNA的剪接是由一个涉及tRNA结合酶的新途径介导的.
- 这一途径绕过了传统的拼接体机械.
- 这些发现揭示了在酵母中的ER压力期间控制基因表达的独特机制.
相关概念视频
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...
Alternative RNA Splicing
Alternative RNA splicing is the regulated splicing of exons and introns to produce different mature mRNAs from a single pre-mRNA. Unlike in constitutive splicing where a single gene produces a single type of mRNA, alternative splicing allows an organism to produce multiple proteins from a single gene and plays an important role in protein diversity.
There are five types of alternative RNA splicing that vary in the ways the pre-mRNA segments are removed or retained in the mature mRNA. The first...
There are five types of alternative RNA splicing that vary in the ways the pre-mRNA segments are removed or retained in the mature mRNA. The first...
The Unfolded Protein Response
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...
Regulation of the Unfolded Protein Response
Inositol-requiring kinase one or IRE1 is the most conserved eukaryotic unfolded protein response (UPR) receptor. It is a type I transmembrane protein kinase receptor with a distinctive site-specific RNase activity. As the binding mechanics of the misfolded proteins with the N-terminal domain of IRE-1 are unclear, three binding models — direct, indirect, and allosteric -- are proposed for receptor activation. Nevertheless, it is known that once a misfolded protein associates with IRE1, it...
Alternative RNA Splicing
Alternative RNA splicing is the regulated splicing of exons and introns to produce different mature mRNAs from a single pre-mRNA. Unlike in constitutive splicing where a single gene produces a single type of mRNA, alternative splicing allows an organism to produce multiple proteins from a single gene and plays an important role in protein diversity.
There are five types of alternative RNA splicing that vary in the ways the pre-mRNA segments are removed or retained in the mature mRNA. The first...
There are five types of alternative RNA splicing that vary in the ways the pre-mRNA segments are removed or retained in the mature mRNA. The first...


