相关实验视频
Updated: Jun 11, 2025

06:03
Delivery of Modified mRNA in a Myocardial Infarction Mouse Model
Published on: June 11, 2020
9.0K
在PLEKHM2 mRNA解码过程中编程的核糖体框架转移会产生一个构成性活跃的蛋白形,支持心肌功能
Gary Loughran1, Raffaella De Pace2, Ningyu Ding3
1School of Biochemistry and Cell Biology, University College Cork, Cork, Ireland.
bioRxiv : the preprint server for biology
|October 7, 2024
概括
科学家们在人类基因PLEKHM2中发现了编程的核糖体框架转移,这是核基因中罕见的事件. 这种框架转移对于正常的心脏细胞功能至关重要.
科学领域:
- 分子生物学分子生物学
- 遗传学 是一个遗传学.
- 细胞生物学 细胞生物学
背景情况:
- 编程核糖体框架转移是一种已知的机制,主要在病毒中,用于改变蛋白质合成.
- 核编码基因中保存的框架转移事件很少见,并且经常引起争论.
- 基因PLEKHM2在细胞过程中发挥作用,但其完整的调节机制尚未完全理解.
研究的目的:
- 研究人类基因PLEKHM2.2.中的编程核糖体框架转移现象.
- 描述这种移事件的机制和功能意义.
- 确定框架转移在PLEKHM2的功能和细胞定位中的作用.
主要方法:
- 在PLEKHM2.2翻译过程中分析mRNA序列和核糖体行为.
- 位点定向的突变发生,以识别移信号.
- 使用显微镜进行细胞局部化研究.
- 在PLEKHM2-Knockout心肌细胞中的功能测试.
主要成果:
- 在人类PLEKHM2基因中,在保存的UCC_UUU_CGG序列中确定了一个+1编程的核糖体框架转移事件.
- 框架转移产生了一个新的C端域,形成一个α螺旋,缓解PLEKHM2.2的自身抑制.
- 框架转移的PLEKHM2与基因素-1结合,用于传输到细胞尖端,独立于ARL8.
- 需要恢复正规和框架转移的PLEKHM2蛋白质,以挽救淘汰心肌细胞的收缩功能.
结论:
- 编程的核糖体框架转移对于PLEKHM2功能和正常的心脏活动至关重要.
- 这一发现扩大了核编码基因中已知的框架转移机制的范围.
- PLEKHM2的取决于移的调节会影响其局部化和细胞功能,特别是在心肌细胞中.
更多相关视频
相关概念视频
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
Ribosome Profiling
3.5K
Ribosome profiling or ribo-sequencing is a deep sequencing technique that produces a snapshot of active translation in a cell. It selectively sequences the mRNAs protected by ribosomes to get an insight into a cell’s translation landscape at any given point in time.
Applications of ribosome profiling
Ribosome profiling has many applications, including in vivo monitoring of translation inside a particular organ or tissue type and quantifying new protein synthesis levels.
The technique...
Applications of ribosome profiling
Ribosome profiling has many applications, including in vivo monitoring of translation inside a particular organ or tissue type and quantifying new protein synthesis levels.
The technique...
3.5K
Leaky Scanning
5.1K
During most eukaryotic translation processes, the small 40S ribosome subunit scans an mRNA from its 5' end until it encounters the first start AUG codon. The large 60S ribosomal subunit then joins the smaller one to initiate protein synthesis. The location of the translation initiation is largely determined by the nucleotides near the start codon as there may be multiple translation initiation sites present on the mRNA. Marilyn Kozak discovered that the sequence RCCAUGG (where R...
5.1K
Translation
14.6K
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...
14.6K
Regulated mRNA Transport
6.3K
In eukaryotes, transcription and translation are compartmentalized; an mRNA is first synthesized in the nucleus and then selectively transported to the cytoplasm for protein synthesis. Before transport, a pre-mRNA undergoes several steps of post-transcriptional modifications including splicing, 5' capping, and the addition of a poly-adenine tail. Various proteins bind to the pre-mRNA during these modifications. The mRNA transport takes place with the help of multiple proteins playing...
6.3K
Ribosomal RNA Synthesis
13.1K
Ribosome synthesis is a highly complex and coordinated process involving more than 200 assembly factors. The synthesis and processing of ribosomal components occurs not only in the nucleolus but also in the nucleoplasm and the cytoplasm of eukaryotic cells.
Ribosome biogenesis begins with the synthesis of 5S and 45S pre-rRNAs by distinct RNA polymerases. The primary transcripts are extensively processed and modified before they are bound and folded by ribosomal proteins and assembly factors,...
Ribosome biogenesis begins with the synthesis of 5S and 45S pre-rRNAs by distinct RNA polymerases. The primary transcripts are extensively processed and modified before they are bound and folded by ribosomal proteins and assembly factors,...
13.1K

