转录适应对杜申肌肉衰竭中的乌托芬进行上调
Lara Falcucci1,2, Christopher M Dooley1,2, Douglas Adamoski1
1Department of Developmental Genetics, Max Planck Institute for Heart and Lung Research, Bad Nauheim, Germany.
Nature
|February 12, 2025
概括
杜申肌肉衰竭 (DMD) 涉及DMD基因的突变. 这项研究揭示了诱导过早终止的编码子通过转录适应触发了乌托芬 (UTRN) 的上调,从而提供了新的治疗途径.
科学领域:
- 分子生物学
- 遗传学
- 生物化学
背景情况:
- 杜申肌肉衰竭 (DMD) 是由DMD基因突变引起的,导致肌肉衰竭.
- 在某些DMD病例中,已知UTRN是一种功能性异构蛋白.
研究的目的:
- 研究DMD中UTRN上调的机制.
- 探索针对mRNA衰变和遗传补偿的治疗策略.
主要方法:
- 使用过早终止子 (PTC) 开发用于DMD的诱导mRNA降解系统.
- 使用拼接切换反感性寡核酸 (ASOs) 来诱导外子跳转和PTC.
- 使用 ribozymes 来研究 UTRN 的上调.
主要成果:
- 将 PTC 引入 DMD mRNA 引发其衰变和随后的 UTRN 上调.
- 阻断无意义介导的mRNA衰变可以逆转UTRN上调.
- 设计用于诱导外子跳转的 ASO 会导致 UTRN 的上调,而读取恢复则会减少它.
结论:
- 转录性适应是一种基于mRNA衰变的机制,对DMD的UTRN上调至关重要.
- 在DMD中诱导基因补偿的ASOs和 ribozymes是潜在的治疗工具.
更多相关视频
06:20Exon Skipping in Directly Reprogrammed Myotubes Obtained from Human Urine-Derived Cells
Published on: May 7, 2020
7.0K
09:11Generation of Induced Pluripotent Stem Cells from Muscular Dystrophy Patients: Efficient Integration-free Reprogramming of Urine Derived Cells
Published on: January 28, 2015
11.2K
相关概念视频
Satellite Stem Cells and Muscular Dystrophy
1.9K
Satellite stem cells or myosatellite cells are quiescent stem cells that Alexander Mauro first identified in 1961. These cells are located between the sarcolemma, the plasma membrane of muscle fibers, and the basal lamina, the connective tissue sheath covering it. These mononucleated cells are activated in response to muscle injury, can transform into myoblasts, and may form or repair muscle fibers. Myosatellite cells can provide additional myonuclei for muscle regeneration or return to a...
1.9K
Master Transcription Regulators
6.9K
Master transcription regulators are regulatory proteins that are predominantly responsible for regulating the expression of multiple genes. Often these genes work in concert to drive a complex process. Activation of a master transcription regulator can lead to a cascade of transcriptional activation necessary for that outcome. These regulators can directly bind to the regulatory sequences of the various genes involved, or they can indirectly regulate transcription by binding to regulatory...
6.9K
Transcription Attenuation in Prokaryotes
15.1K
Transcriptional attenuation occurs when RNA transcription is prematurely terminated due to the formation of a terminator mRNA hairpin structure. Bacteria use these hairpins to regulate the transcription process and control the synthesis of several amino acids including histidine, lysine, threonine, and phenylalanine. Transcription attenuation takes place in the non-coding regions of mRNA.
There are several different mechanisms used to attenuate transcription. In ribosome mediated...
There are several different mechanisms used to attenuate transcription. In ribosome mediated...
15.1K
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
Formation of Muscle Fibers from Myoblasts
4.8K
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...
4.8K
Transcription Factors
75.6K
Tissue-specific transcription factors contribute to diverse cellular functions in mammals. For example, the gene for beta globin, a major component of hemoglobin, is present in all cells of the body. However, it is only expressed in red blood cells because the transcription factors that can bind to the promoter sequences of the beta globin gene are only expressed in these cells. Tissue-specific transcription factors also ensure that mutations in these factors may impair only the function of...
75.6K
