相关实验视频

Updated: Jan 9, 2026

A Scalable, Cell-Based Method for the Functional Assessment of Ube3a Variants

A Scalable, Cell-Based Method for the Functional Assessment of Ube3a Variants

Published on: October 10, 2022

识别5' UTR突变影响神经发育障碍基因翻译和蛋白质生成的方法

Stephen P Plassmeyer¹, Colin P Florian¹, Rebecca Chase¹

¹Department of Genetics, Washington University, St. Louis, MO 63110, USA; Department of Psychiatry, Washington University, St. Louis, MO 63110, USA.

Cell reports methods

|December 4, 2025

概括

在神经发育障碍 (NDD) 中预测功能性非编码突变是困难的. 这项研究开发和基准测试,在5'未翻译区域 (UTR) 识别了100多种突变,这些突变改变了蛋白质翻译.

科学领域:

遗传学是一个遗传学.
神经科学是一个神经科学.
分子生物学分子生物学

背景情况:

编码突变是已知的神经发育障碍 (NDD) 的原因.
评估非编码突变的功能影响,特别是在5'未翻译区域 (UTR) 中,仍然是NDD研究的一个重大挑战.
了解5' UTR突变如何影响基因表达对于诊断和潜在治疗NDD至关重要.

研究的目的:

对各种高通量测试进行基准测试,以评估来自NDD家族的997种突变的功能影响.
识别与NDD相关的基因中的功能5' UTR突变.
研究5' UTRs的细胞类型特定调节原理,特别是在神经元中.

主要方法:

利用来自细胞系的多体体进行大规模并行报告测试 (MPRA) 来评估突变的转化效应.
开发了Cre-依赖的MPRAs用于神经元中的体内评估.
使用患者的淋巴细胞细胞系来测量内源性蛋白质生产的验证结果.

主要成果:

使用基于多元体的MPRAs识别了100多种改变翻译的突变.
发现了功能性5' UTR突变,影响患者衍生细胞系内源性蛋白质的产生.
与其他细胞类型相比,神经元表现出不同的5' UTR调节机制,鉴定出影响神经元转化活动的突变.

结论:

对5' UTR突变影响评估的试验进行了全面的基准测试.
在关键的NDD基因 (例如LRRC4,ZNF644) 中发现了功能性5' UTR突变.
该研究强调了细胞类型特定分析和先进的MPRA技术在NDD研究中的重要性.

关键词:

科普:分子生物学在CP:神经科学.大规模并行记者测试.神经发育的神经发育没有翻译过的地区.

更多相关视频

A Strategy to Identify de Novo Mutations in Common Disorders such as Autism and Schizophrenia

A Strategy to Identify de Novo Mutations in Common Disorders such as Autism and Schizophrenia

Published on: June 15, 2011

A Novel Strategy Combining Array-CGH, Whole-exome Sequencing and In Utero Electroporation in Rodents to Identify Causative Genes for Brain Malformations

A Novel Strategy Combining Array-CGH, Whole-exome Sequencing and In Utero Electroporation in Rodents to Identify Causative Genes for Brain Malformations

Published on: December 1, 2017

相关概念视频

Translation

Translation

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

Translation

Lesson: Translation
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...

Leaky Scanning

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...

Ribosome Profiling

Ribosome Profiling

Ribosome profiling or ribo-sequencing is a deep sequencing technique that produces a snapshot of active translation in a cell. It selectively sequences the mRNAs protected by ribosomes to get an insight into a cell’s translation landscape at any given point in time.
Applications of ribosome profiling
Ribosome profiling has many applications, including in vivo monitoring of translation inside a particular organ or tissue type and quantifying new protein synthesis levels.
The technique...