GAPDH的RNA结合控制了转录稳定性和急性髓性白血病中的蛋白质翻译
bioRxiv : the preprint server for biology
|December 16, 2024
概括
非正规RNA结合蛋白 (ncRBPs) 在急性髓性白血病 (AML) 中至关重要. 研究人员发现,甘-3-酸盐脱酶 (GAPDH) 促进AML细胞增殖,稳定点RNA.
科学领域:
- 分子生物学分子生物学
- 癌症研究 癌症研究
- 血液学 血液学 血液学
背景情况:
- RNA结合蛋白 (RBPs) 的失调是癌症的标志,特别是在急性髓性白血病 (AML) 中,它们调节瘤增殖.
- 虽然正规的RBP已得到充分研究,但非正规RBP (ncRBP) 在AML中的作用在很大程度上是未知的.
- 广泛针对AML是复杂的,需要识别新的治疗目标,如ncRBPs.
研究的目的:
- 确定新的非正规RNA结合蛋白候选物,这些候选物对于急性髓性白血病的生存至关重要.
- 调查在AML中确定的ncRBPs的RNA结合功能和点.
- 阐明ncRBPs对AML细胞增殖和存活有所贡献的机制.
主要方法:
- 基于CRISPR/Cas的查被用于识别AML中的潜在ncRBPs.
- 交叉链接和免疫沉 (CLIP) 用于定义已识别的ncRBPs的全球RNA标组.
- 进行了淘汰实验,以评估ncRBPs对AML细胞通路的功能影响.
主要成果:
- 甘甲基-3-酸盐脱酶 (GAPDH),一种糖解酶,被确定为AML细胞中的促增殖因子.
- CLIP分析揭示了GAPDH的新型RNA标,主要是在5'UTR中,包括GAPDH,RPL13a和PKM转录.
- GAPDH的淘汰影响了参与核糖体生物发生,翻译启动和调节的遗传通路.
- GAPDH与包括其自身mRNA在内的目标转录物结合,显示出稳定作用.
结论:
- GAPDH作为一种非正规的RNA结合蛋白,促进急性髓性白血病的扩散.
- GAPDH通过结合特定的RNA点来调节AML中的关键细胞过程,影响翻译和核糖体生物发生.
- 这些发现为GAPDH在AML中的多面性作用提供了新的见解,突出了其作为治疗点的潜力.
相关概念视频
Leaky Scanning
5.1K
During most eukaryotic translation processes, the small 40S ribosome subunit scans an mRNA from its 5' end until it encounters the first start AUG codon. The large 60S ribosomal subunit then joins the smaller one to initiate protein synthesis. The location of the translation initiation is largely determined by the nucleotides near the start codon as there may be multiple translation initiation sites present on the mRNA. Marilyn Kozak discovered that the sequence RCCAUGG (where R...
5.1K
mRNA Stability and Gene Expression
5.5K
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
5.5K
RNA Stability
33.3K
Intact DNA strands can be found in fossils, while scientists sometimes struggle to keep RNA intact under laboratory conditions. The structural variations between RNA and DNA underlie the differences in their stability and longevity. Because DNA is double-stranded, it is inherently more stable. The single-stranded structure of RNA is less stable but also more flexible and can form weak internal bonds. Additionally, most RNAs in the cell are relatively short, while DNA can be up to 250 million...
33.3K
Translation
14.5K
Translation is the process of synthesizing proteins from the genetic information carried by messenger RNA (mRNA). Following transcription, it constitutes the final step in the expression of genes. This process is carried out by ribosomes, complexes of protein and specialized RNA molecules. Ribosomes, transfer RNA (tRNA), and other proteins produce a chain of amino acids—the polypeptide—as the end product of translation.
Translation Produces the Building Blocks of Life
Proteins are...
Translation Produces the Building Blocks of Life
Proteins are...
14.5K
Chromatin Structure Regulates pre-mRNA Processing
6.9K
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...
6.9K
Regulation of Expression Occurs at Multiple Steps
22.4K
Gene expression can be regulated at almost every step from gene to protein. Transcription is the step that is most commonly regulated. This involves the binding of proteins to short regulatory sequences on the DNA. This association can either promote or inhibit the transcription of a gene associated with the respective sequence.
Transcription results in the generation of precursor (pre-mRNA) that consists of both exons and introns, which needs further processing before being translated to a...
Transcription results in the generation of precursor (pre-mRNA) that consists of both exons and introns, which needs further processing before being translated to a...
22.4K


