在细胞应激和癌症中启动非正规的mRNA翻译
Mélanie Mahé1, Tiffany Rios-Fuller1, Olga Katsara1
1Department of Microbiology, NYU Grossman School of Medicine, New York, NY 10016, USA.
NAR cancer
|June 3, 2024
概括
替代mRNA翻译启动途径对于癌细胞适应压力和转移至关重要. 了解这些非正典机制为瘤学提供了新的治疗点.
科学领域:
- 分子生物学分子生物学
- 细胞生物学 细胞生物学
- 在瘤学瘤学.
背景情况:
- 正规的mRNA翻译启动途径涉及盖结合蛋白eIF4E和启动前复合体.
- 从历史上看,这种正规机制被认为是所有细胞mRNA翻译的解释.
- 最近的发现揭示了替代的,非正典的翻译启动途径.
研究的目的:
- 审查非正规的mRNA转化启动机制在癌症中的新兴作用.
- 突出它们在细胞适应压力和恶性进展中的重要性.
- 在瘤学中确定潜在的新治疗点.
主要方法:
- 关于mRNA翻译启动研究的文献综述.
- 在癌细胞生理学和病理学中分析非正规机制.
- 探索替代翻译和癌症转移之间的联系.
主要成果:
- 在细胞应激条件下,非正典翻译启动通路被激活.
- 这些途径使选择性mRNA翻译成为可能,当正规途径被下调时.
- 癌细胞利用这些机制进行可塑性,入侵,转移和生存.
- 替代翻译启动对于恶性进展期间的表型变化至关重要.
结论:
- 非正规的mRNA翻译启动对于癌细胞适应和转移至关重要.
- 这些替代途径代表了新瘤治疗新的有希望的目标.
- 对这些机制的进一步研究可以推进癌症治疗策略.
相关概念视频
Initiation of Translation
32.5K
Initiating translation is complex because it involves multiple molecules. Initiator tRNA, ribosomal subunits, and eukaryotic initiation factors (eIFs) are all required to assemble on the initiation codon of mRNA. This process consists of several steps that are mediated by different eIFs.
First, the initiator tRNA must be selected from the pool of elongator tRNAs by eukaryotic initiation factor 2 (eIF2). The initiator tRNA (Met-tRNAi) has conserved sequence elements including modified bases at...
First, the initiator tRNA must be selected from the pool of elongator tRNAs by eukaryotic initiation factor 2 (eIF2). The initiator tRNA (Met-tRNAi) has conserved sequence elements including modified bases at...
32.5K
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
14.8K
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...
14.8K
Regulation of Expression Occurs at Multiple Steps
22.6K
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...
22.6K
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


