关于TUT4通过TUT4对Lin28依赖的pre-let-7的橄-尿基化机制的见解
Xiaojie Han1, Seisuke Yamashita1, Kozo Tomita1
1Department of Computational Biology and Medical Sciences, Graduate School of Frontier Sciences, The University of Tokyo, Kashiwa, Chiba 277-8562, Japan.
Nucleic acids research
|January 12, 2026
概括
林28和TUT4/7酶将尿素添加到pre-let-7RNA中,阻止其成熟. 这项研究揭示了这个复杂的结构,显示了TUT4/7/7的结构.
科学领域:
- 分子生物学分子生物学
- 在RNA生物学,RNA生物学.
- 结构生物学 结构生物学
背景情况:
- 林28蛋白通过抑制微RNA生物发生来调节基因表达.
- 终端尿基转移酶4和7 (TUT4/7) 将尿素尾部添加到前体let-7 (pre-let-7) RNA中.
- 这种由 TUT4/7 进行的基-尿基化阻断了Dicer 处理,影响了细胞分化和增殖.
研究的目的:
- 通过 TUT4.4 阐明依赖Lin28的前-let-7 橄-尿基基化酶的结构机制.
- 了解 TUT4 催化模块 (CM) 和 Lin28 相互作用模块 (LIM) 在这个过程中如何合作.
主要方法:
- 低温电子显微镜 (cryo-EM) 用于确定人体TUT4复合物的结构,其中包括Lin28A和化化前-let-7.
- 生物化学分析用于研究不同复杂成分的功能作用.
主要成果:
- 冷-EM结构捕获了pre-let-7 oligo-uridylylation 的延长阶段.
- 林28A在TUT4 LIM中招募了pre-let-7,通过蛋白质-蛋白质相互作用促进了CM的关联.
- CM和LIM稳定了pre-let-7的双链茎,将其3'端定位在催化部位,用于过程性尿素尾部延伸.
结论:
- TUT4 LIM 作为一个稳定的,与 Lin28A 合作,以确保 pre-let-7 的高效和过程性化.
- 这种结构洞察力为Lin28-TUT4相互作用如何调节let-7生物发生和下游细胞过程提供了机械的理解.
相关概念视频
Covalently Linked Protein Regulators
8.6K
Proteins can undergo many types of post-translational modifications, often in response to changes in their environment. These modifications play an important role in the function and stability of these proteins. Covalently linked molecules include functional groups, such as methyl, acetyl, and phosphate groups, and also small proteins, such as ubiquitin. There are around 200 different types of covalent regulators that have been identified.
These groups modify specific amino acids in a protein....
These groups modify specific amino acids in a protein....
8.6K
Regulation of Expression Occurs at Multiple Steps
25.7K
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...
25.7K
Regulation of Expression at Multiple Steps
1.3K
The gene expression in cells is regulated at different stages: (i) transcription, (ii) RNA processing, (iii) RNA localization, and (iv) translation. Transcriptional regulation is mediated by regulatory proteins such as transcription factors, activators, or repressors—these control gene expression by initiating or inhibiting the transcription of genes. Once a precursor or pre-mRNA is produced, it undergoes post-transcriptional modification, including 5' capping, splicing, and the...
1.3K
Pre-mRNA Processing: Modification of pre-mRNA Ends
13.5K
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 (7-methyl guanosine). This 5' cap helps...
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 (7-methyl guanosine). This 5' cap helps...
13.5K
pre-mRNA Processing
57.0K
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...
57.0K
Transfer RNA Synthesis
13.2K
One of the unique features of tRNA is the presence of modified bases. In some tRNAs, modified bases account for nearly 20% of the total bases in the molecule. Altogether, these unusual bases protect the tRNA from enzymatic degradation by RNases.
Each of these chemical modifications is carried by a specific enzyme, post-transcription. All of these enzymes have unique base and site-specificity. Methylation, the most common chemical modification, is carried by at least nine different enzymes, with...
Each of these chemical modifications is carried by a specific enzyme, post-transcription. All of these enzymes have unique base and site-specificity. Methylation, the most common chemical modification, is carried by at least nine different enzymes, with...
13.2K


