外因子结合复合体通过"盾牌效应"影响NFATc1 m6A分布来调节骨质细胞诱导的骨质再吸收
Bao Sun1, Jin-Gang Yang2, Zhe Wang3
1Department of Oral Pathology, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine; College of Stomatology, Shanghai Jiao Tong University; National Center for Stomatology; National Clinical Research Center for Oral Diseases; Shanghai Key Laboratory of Stomatology, Shanghai, China.
Clinical and translational medicine
|March 7, 2025
概括
异构结复合体 (EJCs) 屏蔽NFATc1 m6A甲基化部位,调节基因分布并抑制骨质细胞分化. 这种机制保留了骨质,并为骨质疏松症治疗提供了目标.
科学领域:
- 分子生物学分子生物学
- 表观遗传学 在表观遗传学中,表观遗传学是指表观遗传学.
- 基因规则 基因规则
背景情况:
- N6-甲基氨酸 (m6A) 修饰在转录组上具有区域选择性,有利于长长的外显子和停止的编码子.
- 控制m6A甲基化选择性的精确机制仍未得到充分研究.
研究的目的:
- 阐明m6A甲基化在NFATc1基因上的分布特征和调控机制.
- 调查外结综合体 (EJC) 在m6A位点选择性中的作用.
主要方法:
- 使用了meRIP测序,mRNA测序和 luciferase 记者测试.
- 雇佣了CRISPR/Cas9条件淘汰小鼠来研究NFATc1 m6A的分布.
主要成果:
- 通过METTL14介导的NFATc1的m6A甲基化对于骨质细胞分化和骨质再吸收至关重要.
- EJCs表现出一种"屏蔽效应",保护短外子片段 (50-200 nt) 内的m6A位点免受过甲基化和降解.
- 这种保护作用在较长的外子片段 (>300 nt) 或3' UTR区域中丧失,其中YTHDF2促进了转录降解.
结论:
- EJCs作为"盾牌"来决定NFATc1基因的m6A区域选择性.
- EJCs通过影响甲基化和降解来调节NFATc1mRNA水平,从而抑制骨质细胞分化并保持骨质.
- 研究结果提供了对骨质疏松症潜在治疗点的见解.
相关概念视频
Regulation of Nuclear Protein Sorting
2.3K
Nuclear protein sorting regulates nucleus composition and gene expression, crucial for determining the fate of a eukaryotic cell. Hence, the entry and exit of molecules across the nuclear envelope is a tightly controlled process. Nuclear protein sorting can be inhibited by one of the following ways: 1) masking cargo signal sequences, 2) modifying the nuclear receptor's affinity for cargo, 3) controlling the nuclear pore size, 4) retaining the cargo during its transit to the cytosol or the...
2.3K
Osteoclasts in Bone Remodeling
2.8K
Osteoclasts are cells responsible for bone resorption and remodeling. They originate from hematopoietic progenitor cells present in the bone marrow. Numerous progenitor cells fuse to form multinucleated cells, each with 10-20 nuclei. A single osteoclast has a diameter of 150 to 200 µM. These cells have ruffled borders that break down the underlying bone tissue and release minerals such as calcium into the blood in bone resorption. Osteoclasts cling to bones with their ruffled edges during...
2.8K
NF-κB-dependent Signaling Pathway
7.2K
The transcription factor NF-κB was discovered in 1986 in the lab of Nobel laureate Professor David Baltimore, for its interaction with the immunoglobulin light chain enhancer in B-cells. After more than three decades of study, it is now evident that NF-κB regulates the expression of over 100 genes. Most of these genes play an essential role in the innate and adaptive immune responses as well as the inflammatory responses of animals.
NF-κB-dependent Signaling Mechanism
The...
NF-κB-dependent Signaling Mechanism
The...
7.2K
Regulation of Expression at Multiple Steps
862
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...
862
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
Receptor Downregulation in MVBs
2.0K
Multivesicular bodies (MVBs) are mature endosomes that sort ubiquitinated proteins and then fuse with lysosomes to degrade the sorted proteins. Epidermal growth factor (EGF) and its receptor (EGFR) form a complex that can be internalized through endocytosis, sorted into an MVB, and later degraded.
The EGFR can initiate signaling pathways that lead to cell proliferation, migration, and differentiation. Overexpression of EGFR stimulates cells to proliferate. Excessive EGFR...
The EGFR can initiate signaling pathways that lead to cell proliferation, migration, and differentiation. Overexpression of EGFR stimulates cells to proliferate. Excessive EGFR...
2.0K


