通过调节hsa-miR-452626的N6-甲基氨酸依赖性初级处理,METTL3促进骨质生成
Yidan Song1, Hongyu Gao1, Yihua Pan2
1State Key Laboratory of Oral Diseases, National Center for Stomatology, National Clinical Research Center for Oral Diseases, Department of Orthodontics, West China Hospital of Stomatology, Sichuan University, Chengdu 610041, Sichuan, China.
Stem cells (Dayton, Ohio)
|January 5, 2025
概括
甲基转移酶类3 (METTL3) 通过调节N6-甲基氨酸 (m6A) 修饰pri-miRNAs,特别是hsa-miR-4526,从而抑制TUBB3表达来增强骨形成,从而促进骨质生成.
科学领域:
- 干细胞生物学 干细胞生物学
- 表观遗传学 在表观遗传学中,表观遗传学是指表观遗传学.
- 骨生物学 骨生物学
背景情况:
- N6-甲基氨酸 (m6A) 修饰在pri-miRNA成熟和骨质生成中的作用尚未完全理解.
- 研究人类脂肪衍生干细胞 (hASC) 骨质生成中的甲基转移酶类似3 (METTL3) 的机制至关重要.
研究的目的:
- 阐明hASC骨质生成中由METTL3修改的primi-miRNA m6A的功能和调节机制.
- 为了确定参与这个过程的特定的primiRNAs.
主要方法:
- 甲基化RNA免疫沉降测序 (MeRIP-seq) 用于识别甲基化pri-miRNAs.
- 定量实时聚合酶连锁反应 (qRT-PCR) 和共同免疫沉以确认相互作用.
- 双 luciferase 报告员测定和救援实验以验证调节途径.
主要成果:
- 发现METTL3在体内和体外都能促进骨质生成.
- 在 pri-miR4526/5190 的 METTL3-介导的 m6A 修改促进了 hsa-miR-4526 处理.
- Hsa-miR-4526通过抑制TUBB3表达来促进骨质生成,这通常会抑制hASC骨质生成.
结论:
- 这项研究揭示了primi-miRNA m6A修饰的新型机制,通过METTL3/hsa-miR-4526/TUBB3轴调节hASC骨质生成.
- 通过准这种途径,提出了一种新的骨缺陷修复策略.
更多相关视频
相关概念视频
01:22MicroRNAs
3.0K
MicroRNA (miRNA) are short, regulatory RNA transcribed from introns (non-coding regions of a gene) or intergenic regions (stretches of DNA present between genes). Several processing steps are required to form biologically active, mature miRNA. The initial transcript, called primary miRNA (pri-mRNA), base-pairs with itself, forming a stem-loop structure. Within the nucleus, an endonuclease enzyme, called Drosha, shortens the stem-loop structure into hairpin-shaped pre-miRNA. After the pre-miRNA...
3.0K
02:24Regulation 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
01:23Regulation of Expression at Multiple Steps
868
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...
868
02:41Chromatin 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
01:16TGF - β Signaling Pathway
7.2K
The TGF-β signaling pathway regulates cell growth, differentiation, adhesion, motility, and development. TGF-β ligands that induce TGF-β signaling are synthesized in their latent form. Several proteases or cell surface receptors such as integrins act upon the latent form, releasing the active ligand. There are three types of mammalian TGF-βs: (TGF-β1, TGF-β2, and TGF-β3) that bind as homodimers or heterodimers to TGF-β receptors. The TGF-β receptors...
7.2K
02:51mRNA 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