RNA结合蛋白Nocte通过促进长期上游开放阅读框架的mRNA上的翻译重新启动来调节Drosophila的发育
Tianyi Zhang1, Yutong Xue1, Shuaikun Su1
1Laboratory of Genetics and Genomics, National Institute on Aging, Intramural Research Program, National Institutes of Health, Baltimore, MD 21224, USA.
Nucleic acids research
|November 24, 2023
概括
诺克特蛋白对果眼睛的发育至关重要,因为它增强了基因翻译. 它的干扰会影响发育,并与精神分裂症等人类神经系统疾病有关.
科学领域:
- 分子生物学分子生物学
- 发展生物学 发展生物学
- 遗传学 遗传学 是一个
背景情况:
- 具有内在无序区域 (IDRs) 的RNA结合蛋白 (RBPs) 与人类疾病有关.
- 对于许多RBP,特别是具有IDR的RBP,其精确的作用机制尚未完全理解.
- 了解RBP的功能是解读发育过程和疾病发病的关键.
研究的目的:
- 为了研究RBP Nocte在Drosophila melanogaster发育中的功能.
- 阐明诺克特调节基因表达的分子机制.
- 探索诺克特功能与人类神经系统疾病之间的潜在联系.
主要方法:
- 利用Drosophila melanogaster作为遗传研究的模型生物.
- 执行了基因淘汰和Nocte基因的眼睛特异性枯竭.
- 分析了mRNA翻译效率,专注于上游开放阅读框架 (uORF).
- 研究了涉及Nocte和转化因子的蛋白质-蛋白质相互作用.
主要成果:
- 诺克特对多索菲拉眼睛发育至关重要;它缺少会导致致死性或损伤眼睛形态.
- 诺克特特别增强含有长上游开放阅读框架 (uORF) 的mRNA的翻译.
- 诺克特促进了uORF下游的翻译重新启动,抵消了翻译抑制.
- 诺克特通过其BAT2领域与转化因子eIF3和Rack1相互作用,这对其功能至关重要.
结论:
- 在发育过程中,诺克特在转化水平上调节基因表达起着至关重要的作用.
- 诺克特蛋白促进翻译重新启动,克服uORF介导的抑制.
- 诺克特功能失调可能会导致发育缺陷和神经系统疾病,正如精神分裂症患者中发现的人类骨干突变所表明的那样.
相关概念视频
Types of RNA
5.8K
Three main types of RNA are involved in protein synthesis: messenger RNA (mRNA), transfer RNA (tRNA), and ribosomal RNA (rRNA). These RNAs perform diverse functions and can be broadly classified as protein-coding or non-coding RNA. Non-coding RNAs play important roles in regulating gene expression in response to developmental and environmental changes. Non-coding RNAs in prokaryotes can be manipulated to develop more effective antibacterial drugs for human or animal use.
RNA Performs Diverse...
RNA Performs Diverse...
5.8K
RNA Polymerase II Accessory Proteins
9.2K
Proteins that regulate transcription can do so either via direct contact with RNA Polymerase or through indirect interactions facilitated by adaptors, mediators, histone-modifying proteins, and nucleosome remodelers. Direct interactions to activate transcription is seen in bacteria as well as in some eukaryotic genes. In these cases, upstream activation sequences are adjacent to the promoters, and the activator proteins interact directly with the transcriptional machinery. For example, in...
9.2K
Regulation of Expression at Multiple Steps
919
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...
919
Initiation of Translation
33.7K
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...
33.7K
piRNA - Piwi-interacting RNAs
6.9K
PIWI-interacting RNAs, or piRNAs, are the most abundant short non-coding RNAs. More than 20,000 genes have been found in humans that code for piRNAs while only 2000 genes have been found for miRNAs. piRNAs can act at the transcriptional and post-transcriptional levels and have a vital role in silencing transposable elements present in germ cells. They are also involved in epigenetic silencing and activation. Previously, they were thought to function only in germ cells but new evidence suggests...
6.9K
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


