葡萄糖解离DDX21二分体以调节mRNA拼接和组织分化
Weili Miao1, Douglas F Porter1, Vanessa Lopez-Pajares1
1Program in Epithelial Biology, Stanford University School of Medicine, Stanford, CA, USA.
Cell
|January 7, 2023
概括
葡萄糖通过与DDX21RNA酶结合来调节蛋白相互作用和RNA剪接. 这种依赖葡萄糖的机制对表皮分化和关键的分化基因的表达至关重要.
科学领域:
- 分子生物学
- 生物化学
- 细胞分化
背景情况:
- 葡萄糖是主要的能量来源,但其在蛋白质相互作用中的调节作用,特别是在细胞分化过程中,被低估了.
- 细胞内葡萄糖水平在分化过程中波动,这表明超出了能量供应的潜在信号作用.
研究的目的:
- 研究葡萄糖在控制蛋白质相互作用中的不知名作用,特别关注其在与分化相关的细胞内葡萄糖升高期间的作用.
- 使用DDX21RNA酶作为模型,阐明葡萄糖调节RNA结合蛋白 (RBPs) 的功能.
主要方法:
- 使用阿齐多-葡萄糖点击化学来识别结合葡萄糖的RBP.
- 描述了葡萄糖与DDX21RNA酶的相互作用,包括其ATP结合域.
- 在表皮分化过程中评估葡萄糖对DDX21构成,酶活性,二元化和细胞局部化的影响.
- 研究了DDX21与特定的mRNA基因的结合及其在分化相关基因的mRNA前拼接中的作用.
主要成果:
- 葡萄糖直接与DDX21的ATP结合域结合,改变其构造,抑制其酶活性,并促进二聚体解离.
- 在分化过程中细胞内葡萄糖的升高会触发DDX21从细胞核转移到细胞核中,在那里它会与RNA拼接因子形成复合物.
- DDX21以葡萄糖依赖的方式与mRNA内基因中的特定SCUGSDGC基因结合,促进基本的分化基因 (GRHL3,KLF4,OVOL1,RBPJ) 的拼接.
结论:
- 葡萄糖通过调节DDX21二分化和活性来作为RNA酶功能的生化调节剂.
- 这种依赖葡萄糖的机制对于控制RNA拼接和促进组织分化至关重要.
- 发现了一种新的生化途径,将细胞代谢与基因调节联系起来.
相关概念视频
Chromatin Structure Regulates pre-mRNA Processing
7.1K
In eukaryotic cells, nascent mRNA transcripts need to undergo many post-transcriptional modifications to reach the cell cytoplasm and translate into functional proteins. For a long time, transcription and pre-mRNA processing were considered two independent events that occur sequentially in the cell. However, it has now been well established that transcription and pre-mRNA processing are two simultaneous processes that are precisely regulated inside the cell.
The chromatin structure, especially...
The chromatin structure, especially...
7.1K
RNA Splicing
56.6K
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...
56.6K
Alternative RNA Splicing
21.6K
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...
21.6K
Chromatin Structure and RNA Splicing
2.8K
2.8K
mRNA Stability and Gene Expression
5.7K
The structure and stability of mRNA molecules regulates gene expression, as mRNAs are a key step in the pathway from gene to protein. In eukaryotes, the half-life of mRNA varies from a few minutes up to several days. mRNA stability is essential in growth and development. The absence of the proteins regulating its stability, such as tristetraprolin in mice, can cause systemic issues, including bone marrow overgrowth, inflammation, and autoimmunity.
Cis-acting Elements involved in mRNA stability
Cis-acting Elements involved in mRNA stability
5.7K
What is Gene Expression?
8.9K
A gene is a stretch of DNA that serves as the blueprint for functional RNAs and proteins. Since DNA is comprised of nucleotides and proteins are comprised of amino acids, a mediator is required to convert the information encoded in DNA into proteins. This mediator is the messenger RNA (mRNA). mRNA copies the blueprint from DNA by a process called transcription. In eukaryotes, transcription occurs in the nucleus by complementary base-pairing with the DNA template. The mRNA is then...
8.9K


