细胞质PXR通过结合mRNA和调节它们的稳定性来调节葡萄糖代谢
Xiaofei Wang1, Zehua Wang1, Sihan Li1
1Center for Pharmacogenetics, Department of Pharmaceutical Sciences, University of Pittsburgh, Pittsburgh, PA, USA.
Nature structural & molecular biology
|August 12, 2025
概括
孕妇X受体 (PXR) 作为RNA结合蛋白,稳定细胞质中的特定mRNA. 这种新发现的功能会影响新陈代谢的重编程,并促进癌细胞的增殖.
科学领域:
- 分子生物学分子生物学
- 癌症生物学 癌症生物学
- 生物化学 生化学
背景情况:
- 孕妇X受体 (PXR) 是一种核受体,被认为是异生物代谢的主调节器.
- PXR的既定作用涉及到核内部的转录调节.
研究的目的:
- 研究PXR在基因调节中的潜在非转录作用.
- 描述PXR与mRNA的相互作用及其在细胞过程中的功能后果.
主要方法:
- 增强紫外交联和免疫沉降 (eCLIP) 以识别与PXR结合的mRNAs.
- 在各种癌细胞系和正常肝脏组织中分析PXR结合的转录.
- 研究细胞质PXR与RNA结合蛋白的相互作用及其对mRNA稳定性的影响.
主要成果:
- PXR与mRNA结合,包括那些参与代谢重编程和脂质代谢的mRNA.
- 细胞质PXR通过其指域结合并稳定具有C+G丰富序列的成熟mRNA.
- PXR与RNase抑制剂RNH1相互作用,以调节RNA的稳定性.
- 在结直肠癌中,细胞质PXR稳定SLC2A1mRNA,增强葡萄糖吸收,增殖和癌症的发展.
结论:
- PXR作为细胞质中的RNA结合蛋白,独立于其核转录作用.
- 细胞质PXR调节mRNA的稳定性,影响细胞代谢和癌症的进展.
- 这项研究揭示了影响RNA生物学的PXR介导基因调节的新维度.
相关概念视频
Cell Specific Gene Expression
13.9K
Multicellular organisms contain a variety of structurally and functionally distinct cell types, but the DNA in all the cells originated from the same parent cells. The differences in the cells can be attributed to the differential gene expression. Liver cells, whose functions include detoxification of blood, production of bile to metabolize fats, and synthesis of proteins essential for metabolism, must express a specific set of genes to perform their functions. Gene expression also varies with...
13.9K
cAMP-dependent Protein Kinase Pathways
6.6K
Cyclic Adenosine Monophosphate (cAMP) is an essential second messenger that activates protein kinase A (PKA) and regulates various biological processes. A single epinephrine molecule binds to GPCR and activates several heterotrimeric G proteins, each stimulating multiple adenylyl cyclase, amplifying the signal, and synthesizing large numbers of cAMP molecules. Small changes in cAMP concentration affect PKA activity. The binding of four cAMP molecules induces a conformational change in PKA,...
6.6K
Glucose Homeostasis: Regulation of Blood Glucose
2.5K
Carbohydrates consumed through foods are converted into glucose, a crucial energy source for the body. In the prandial state, high blood glucose levels stimulate the secretion of insulin from the pancreas. Insulin inhibits hepatic glucose production and stimulates glucose uptake and metabolism by muscle and adipose tissue. The excess glucose is converted into glycogen and stored in the liver and muscles.
During fasting, when blood glucose levels are low, the pancreas secretes glucagon. it...
During fasting, when blood glucose levels are low, the pancreas secretes glucagon. it...
2.5K
Global Regulatory Systems
72
Global regulatory systems in bacteria enable rapid and coordinated responses to environmental changes by integrating sensory inputs with gene expression, ensuring efficient adaptation to fluctuating conditions. Key global regulatory mechanisms include regulons, two-component systems, sigma factors, and secondary messengers.Regulons and Global RegulatorsA regulon is a collection of genes and operons controlled by a common global regulator. These regulators enable bacteria to prioritize resource...
72
Regulation of Expression at Multiple Steps
1.0K
The gene expression in cells is regulated at different stages: (i) transcription, (ii) RNA processing, (iii) RNA localization, and (iv) translation. Transcriptional regulation is mediated by regulatory proteins such as transcription factors, activators, or repressors—these control gene expression by initiating or inhibiting the transcription of genes. Once a precursor or pre-mRNA is produced, it undergoes post-transcriptional modification, including 5' capping, splicing, and the...
1.0K
GPCRs Regulate Adenylyl Cylase Activity
5.9K
Some GPCRs transmit signals through adenylyl cyclase (AC), a transmembrane enzyme. AC helps synthesize second messenger cyclic adenosine monophosphate (cAMP). AC catalyzes cyclization reaction and converts ATP to cAMP by releasing a pyrophosphate. The pyrophosphate is further hydrolyzed to phosphate by the enzyme pyrophosphatase, which drives cAMP synthesis to completion. However, cAMP is rapidly degraded to 5′ AMP by the enzymes phosphodiesterase (PDE), preventing overstimulation of...
5.9K


