结合NEDD4的蛋白质N4BP1通过编码序列来降解mRNA基质,这种编码序列独立于无意义介导的衰变
Wen Zheng1, Jinjing Guo1, Shuyan Ma1
1Department of Pathogenic Biology, School of Medicine, Nantong University, Nantong, China; Laboratory of Medical Science, School of Medicine, Nantong University, Nantong, China.
The Journal of biological chemistry
|November 4, 2024
概括
N4BP1通过编码序列 (CDS) 而不是3'UTR来降解mRNA目标. 这种新的CDS-依赖的mRNA循环机制涉及特定的动机,需要N4BP1
科学领域:
- 分子生物学分子生物学
- 基因规则 基因规则
背景情况:
- 3'UTRs是已知的mRNA周转的调节者.
- 编码序列 (CDS) 在mRNA周转中的作用尚不清楚.
- N4BP1是一种具有未定义分子机制的炎症调节剂.
研究的目的:
- 为了研究N4BP1介导的mRNA周转机制.
- 为了确定N4BP1是否通过CDS或3'UTR准mRNA.
- 为了确定N4BP1功能中涉及的特定序列和域.
主要方法:
- 使用各种基质 (Fos-C,Fos-B,Jun-B,CXCL1) 的mRNA降解试验.
- 序列映射用于识别CDS中的关键动机.
- 对N4BP1.1的域删除和点突变研究.
- 无意中介衰变 (NMD) 缺陷细胞系实验.
主要成果:
- N4BP1主要通过CDS降解mRNA目标,而不是3'UTR.
- 在Fos-C CDS中的33-nt多C丰富基因对N4BP1活动至关重要.
- N4BP1的K同质性和YacP类核酶域都对mRNA限制至关重要.
- 通过N4BP1介导的营业额独立于NMD和LUC7L3.
结论:
- N4BP1作为一种内啡核糖酶起作用.
- N4BP1通过CDS调解mRNA降解,特别是那些具有C丰富基因的基因.
- 这揭示了一个新的CDS-依赖的mRNA周转途径.
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
Nuclear Export of mRNA
7.6K
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...
7.6K
mRNA 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
RNA Editing
8.9K
RNA editing is a post-transcriptional modification where a precursor mRNA (pre-mRNA) nucleotide sequence is changed by base insertion, deletion, or modification. The extent of RNA editing varies from a few hundred bases, in mitochondrial DNA of trypanosomes, to a just single base, in nuclear genes of mammals. Even a single base change in the pre-mRNA can convert a codon for one amino acid into the codon for another amino acid or a stop codon. This type of re-coding can significantly affect the...
8.9K
Chromatin 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
pre-mRNA Processing
52.6K
In eukaryotic cells, transcripts made by RNA polymerase are modified and processed before exiting the nucleus. Unprocessed RNA is called precursor mRNA or pre-mRNA to distinguish it from mature mRNA.
Once about 20-40 ribonucleotides have been joined together by RNA polymerase, a group of enzymes adds a “cap” to the 5’ end of the growing transcript. In this process, a 5’ phosphate is replaced by modified guanosine that has a methyl group attached to it (7-Methyl...
Once about 20-40 ribonucleotides have been joined together by RNA polymerase, a group of enzymes adds a “cap” to the 5’ end of the growing transcript. In this process, a 5’ phosphate is replaced by modified guanosine that has a methyl group attached to it (7-Methyl...
52.6K


