选择性地要求Spt4用于扩展的三核酸重复的转录
Chia-Rung Liu1, Chuang-Rung Chang, Yijuang Chern
1Institute of Biochemistry and Molecular Biology, National Yang-Ming University, No. 155, Section 2, Linong Street, Taipei, Taiwan, Republic of China.
Cell
|February 21, 2012
概括
转录延长因子Spt4对于转录长三核酸重复至关重要,这些重复会导致诸如亨廷顿病之类的神经疾病. 抑制其哺乳动物的正方体会减少有毒的蛋白质聚合物.
科学领域:
- 神经科学是一个神经科学.
- 分子生物学分子生物学
- 遗传学 是一个遗传学.
背景情况:
- 亨廷顿病和其他遗传性神经系统疾病的特征是长时间的三核酸重复编码多重胺 (polyQ) 延伸.
- 这些多Q扩张导致导致导致细胞功能障碍的变异蛋白.
研究的目的:
- 为了确定参与长三核酸重复的转录的细胞机制.
- 为了找到这些重复引起的神经系统疾病的潜在治疗点.
主要方法:
- 在S. cerevisiae中进行表型查,以确定恢复polyQ蛋白功能的因素.
- 转录延长因子Spt4.4的突变
- 用RNA测序 (RNA-seq) 分析来评估基因表达.
- 在神经细胞中抑制Supt4h,哺乳动物Spt4的正方体.
主要成果:
- 发现Spt4对于编码和非编码DNA区域中长三核酸重复的转录至关重要.
- SPT4突变选择性地降低了polyQ蛋白质合成,并恢复了酶活性,而不会影响缺乏长polyQ延伸的蛋白质.
- RNA-seq揭示了Spt4对整体基因表达的最小影响.
- 在神经元细胞中抑制Supt4h可以减少突变的亨廷丁蛋白,聚合和毒性,而不会改变全球mRNA合成.
结论:
- 在细胞机制中,Spt4在转录重复的三核酸序列方面发挥着至关重要的作用.
- Supt4h抑制为与扩展的三核酸区域相关的神经系统疾病提供了潜在的治疗策略.
相关概念视频
Transcription Attenuation in Prokaryotes
Transcriptional attenuation occurs when RNA transcription is prematurely terminated due to the formation of a terminator mRNA hairpin structure. Bacteria use these hairpins to regulate the transcription process and control the synthesis of several amino acids including histidine, lysine, threonine, and phenylalanine. Transcription attenuation takes place in the non-coding regions of mRNA.
There are several different mechanisms used to attenuate transcription. In ribosome mediated...
There are several different mechanisms used to attenuate transcription. In ribosome mediated...
Translesion DNA Polymerases
Translesion (TLS) polymerases rescue stalled DNA polymerases at sites of damaged bases by replacing the replicative polymerase and installing a nucleotide across the damaged site. Doing so, TLS allows additional time for the cell to repair the damage before resuming regular DNA replication.
TLS polymerases are found in all three domains of life - archaea, bacteria, and eukaryotes. Of the different classes of TLS polymerases, members of the Y family are fitted with specialized structures that...
TLS polymerases are found in all three domains of life - archaea, bacteria, and eukaryotes. Of the different classes of TLS polymerases, members of the Y family are fitted with specialized structures that...
Non-LTR Retrotransposons
As the name suggests, non-LTR retrotransposons lack the long terminal repeats characteristic of the LTR retrotransposons. Additionally, both LTR and non-LTR retrotransposons use distinct mechanisms of mobilization. Non-LTR retrotransposons are further divided into two classes - Long interspersed nuclear elements (LINEs) and short interspersed nuclear elements (SINEs), both of which occur abundantly in most mammals, including humans. Some of the active non-LTR retrotransposons in humans are L1...
Single Nucleotide Polymorphisms-SNPs
A single nucleotide polymorphism or SNP is a single nucleotide variation at a specific genomic position in a large population. It is the most prevalent type of sequence variation found in the human genome. Point mutations that occur in more than 1% of the population qualify as SNPs. These are present once every 1000 nucleotides on an average in the human genome. Replacement of a purine with another purine (A/G) or a pyrimidine with another pyrimidine (C/T) is known as a transition. In contrast,...
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...
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...

