由Ythdf2介导的STK11mRNA衰变通过抑制AMPK/mTOR通路来支持肌形成
Kaiping Deng1, Zhipeng Liu1, Xiaodan Li1
1Institute of Sheep and Goat Science, Nanjing Agricultural University, Nanjing 210095, China; Institute of Haimen Goat Industry, Nanjing Agricultural University, Nanjing 210095, China.
International journal of biological macromolecules
|October 26, 2023
概括
Ythdf2蛋白通过降解STK11mRNA来促进骨肌肉的发育,这抑制了AMPK/mTOR通路. 这种RNA修饰机制对于肌肉发育至关重要.
科学领域:
- 分子生物学分子生物学
- 发展生物学 发展生物学
- 在RNA生物学,RNA生物学.
背景情况:
- 在哺乳动物发育过程中,N6-甲基氨酸 (m6A) 修饰会在转录后调节mRNA.
- 一种m6A读者蛋白质Ythdf2调解mRNA降解,但其在骨肌肉发育中的作用尚不清楚.
研究的目的:
- 研究Ythdf2在骨肌肉发育中的功能和机制.
- 阐明Ythdf2在肌细胞增殖和分化中的作用.
主要方法:
- Ythdf2敲击和肌源性差异化诱导.
- 高通量测序,共免疫沉降 (Co-IP) 和RNA免疫沉降 (RIP) 测试.
- 对AMPK/mTOR信号通路的分析.
主要成果:
- 在肌体分化过程中,Ythdf2的表达增加;它的敲击抑制了肌细胞增殖和分化.
- Ythdf2与STK11mRNA中的m6A位点结合,通过Ago2复合体促进其降解.
- 通过抑制AMPK/mTOR通路,STK11的下调部分挽救了Ythdf2的淘汰效应.
结论:
- Ythdf2介导的STK11mRNA衰变,依赖于Ago2系统,通过抑制AMPK/mTOR通路来驱动骨肌发生.
- 这项研究阐明了RNA甲基化在肌体发生调节中的作用,为未来的研究提供了洞察力.
更多相关视频
相关概念视频
PI3K/mTOR/AKT Signaling Pathway
3.6K
The mammalian target of rapamycin (mTOR) is a serine/threonine kinase that regulates growth, proliferation, and cell survival in response to hormones, growth factors, or nutrient availability. This kinase exists in two structurally and functionally distinct forms: mTOR complex 1 (mTORC1) and mTOR complex 2 (mTORC2). The first form (mTORC1) is composed of a rapamycin-sensitive Raptor and proline-rich Akt substrate, PRAS40. In contrast, mTORC2 consists of a...
3.6K
mTOR Signaling and Cancer Progression
3.8K
The mammalian target of rapamycin or mTOR protein was discovered in 1994 due to its direct interaction with rapamycin. The protein gets its name from a yeast homolog called TOR. The mTOR protein complex in mammalian cells plays a major role in balancing anabolic processes such as the synthesis of proteins, lipids, and nucleotides and catabolic processes, such as autophagy in response to environmental cues, such as availability of nutrients and growth factors.
The mTOR pathway or the...
The mTOR pathway or the...
3.8K
Nonsense-mediated mRNA Decay
10.6K
The Upf proteins that carry out nonsense-mediated decay (NMD) are found in all eukaryotic organisms, including humans. Each protein has an individual role, but they need to work in collaboration. Upf1 is an ATP-dependent RNA helicase that unwinds the RNA helix. Because Upf1 can unwind any RNA, Upf2 and Upf3 are required to help Upf1 discriminate between nonsense and normal mRNAs.
Usually, Upf3 binds to an Exon Junction Complex (EJC) at mRNA splice sites. If a ribosome fully translates the mRNA,...
Usually, Upf3 binds to an Exon Junction Complex (EJC) at mRNA splice sites. If a ribosome fully translates the mRNA,...
10.6K
Formation of Muscle Fibers from Myoblasts
4.9K
De novo myogenesis, or the formation of muscle fibers, begins during the early embryonic stages. The skeletal muscle is formed from somites– blocks of embryonic cell layers. The somites are further divided into dermatomes, myotomes, sclerotomes, and syndetomes. Among these, the myotomes give rise to muscle fibers.
Muscle progenitor cells (MPCs) are formed from the myotomes. MPCs express genes that encode the transcription factors Pax3 and Pax7. Along with Pax 3/7, other transcription...
Muscle progenitor cells (MPCs) are formed from the myotomes. MPCs express genes that encode the transcription factors Pax3 and Pax7. Along with Pax 3/7, other transcription...
4.9K
mRNA Stability and Gene Expression
5.6K
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
5.6K
Nuclear Export of mRNA
7.7K
Before mRNAs are exported to the cytoplasm, it is crucial to check each mRNA for structural and functional integrity. Eukaryotic cells use several different mechanisms, collectively known as mRNA surveillance, to look for irregularities in mRNAs. Irregular or aberrant mRNA are rapidly degraded by various enzymes. If a defective mRNA escapes the surveillance, it would be translated into a protein which would either be non-functional or not function properly. One of the primary irregularities in...
7.7K


