在人类3' UTR中量化负选择揭示了RNA结合蛋白的受约束标
Scott D Findlay1, Lindsay Romo1,2, Christopher B Burge3
1Department of Biology, Massachusetts Institute of Technology, Cambridge, MA, 02142, USA.
Nature communications
|January 3, 2024
概括
研究人员通过分析人类遗传数据,确定了功能性3' 未翻译区域 (3' UTR) 变异. 他们开发了一种检测负选择的新方法,在强大的进化压力下揭示了关键的RNA结合蛋白位点和miRNA点.
科学领域:
- 基因组学就是基因组学.
- 分子生物学分子生物学
- 进化生物学 进化生物学
背景情况:
- 在3' 未翻译区域 (3' UTR) 的非编码变异与表型相关,但很难在功能上识别.
- 这些变异可能通过与RNA结合蛋白 (RBPs) 的相互作用来通过转录后调节基因表达.
研究的目的:
- 在人类基因组中强烈负选择下识别功能性3' UTR变异.
- 开发和验证一种方法来量化非编码地区的负选择.
主要方法:
- 利用了基因组聚合数据库 (gnomAD) 的等位基因频率.
- 开发了基因间可变性调整比例单元 (iMAPS) 来量化负选择.
- 集成iMAPS与RBPs,miRNA目标和多基化信号 (PAS) 的体外和体外结合数据.
主要成果:
- 在强烈负选择下,在3' UTR中识别了数千个gnomAD变体,与误解编码变体相似.
- 在显著的进化约束下确定了精确的RBP结合部位,miRNA点部位和PAS.
- 发现,在最常用的PAS上游的核心3' UTR区域的地点表现出最强的选择.
结论:
- 这项研究增强了对人类基因作用的进化选择的理解.
- 开发的方法为解释人类3' UTRs中的遗传变异提供了经过验证的框架.
- 在3' UTR中确定了在强大的进化压力下面的特定监管元素.
相关概念视频
Types of RNA
Overview
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 the regulation of 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...
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 the regulation of 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...
RNA Interference
RNA interference (RNAi) is a process in which a small non-coding RNA molecule blocks the post-transcriptional expression of a gene by binding to its messenger RNA (mRNA) and preventing the protein from being translated.
This process occurs naturally in cells, often through the activity of genomically-encoded microRNAs. Researchers can take advantage of this mechanism by introducing synthetic RNAs to deactivate specific genes for research or therapeutic purposes. For example, RNAi could be used...
This process occurs naturally in cells, often through the activity of genomically-encoded microRNAs. Researchers can take advantage of this mechanism by introducing synthetic RNAs to deactivate specific genes for research or therapeutic purposes. For example, RNAi could be used...
Leaky Scanning
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 stands for...
RNA Interference
RNA interference (RNAi) is a process in which a small non-coding RNA molecule blocks the post-transcriptional expression of a gene by binding to its messenger RNA (mRNA) and preventing the protein from being translated.
This process occurs naturally in cells, often through the activity of genomically-encoded microRNAs. Researchers can take advantage of this mechanism by introducing synthetic RNAs to deactivate specific genes for research or therapeutic purposes. For example, RNAi could be used...
This process occurs naturally in cells, often through the activity of genomically-encoded microRNAs. Researchers can take advantage of this mechanism by introducing synthetic RNAs to deactivate specific genes for research or therapeutic purposes. For example, RNAi could be used...
Types of RNA
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...
Nucleic Acid Structure
The pentose sugar in DNA is deoxyribose, while in RNA the pentose sugar is ribose. The difference between the sugars is the presence of the hydroxyl group on the ribose's second carbon and a hydrogen on the deoxyribose's second carbon. The phosphate residue attaches to the hydroxyl group of the 5′ carbon of one sugar and the hydroxyl group of the 3′ carbon of the sugar of the next nucleotide, which forms a 5′ to 3′ phosphodiester linkage.
DNA Structure
DNA has a double-helix structure. The...
DNA Structure
DNA has a double-helix structure. The...


