相关实验视频

Updated: Jun 16, 2025

Author Spotlight: Polysome Profiling Protocol for Studying Translational Regulation in Arabidopsis Under Heat Stress

Author Spotlight: Polysome Profiling Protocol for Studying Translational Regulation in Arabidopsis Under Heat Stress

Published on: October 11, 2024

在适应环境挑战时,YTHDF1通过m6AmRNA甲基化调解转化控制

Zhuoyue Shi¹, Kailong Wen², Zhongyu Zou³

¹The Department of Neurobiology, University of Chicago, Chicago, IL 60637, USA.

bioRxiv : the preprint server for biology

|August 16, 2024

概括

N6-甲基氨酸 (m6A) RNA修饰途径,特别是涉及YTHDF1,对于成年神经元适应至关重要. 破坏这种途径会损害多巴胺神经元中的学习和蛋白质合成.

科学领域:

神经科学是一个神经科学.
分子生物学分子生物学
表观遗传学在表观遗传学中,表观遗传学是指表观遗传学.

背景情况:

动物通过长期的分子和行为修改来适应环境变化.
N6-甲基氨酸 (m⁶A) 的mRNA修改可以在转录后调节基因表达.
在成年神经元中m6A的作用仍未得到充分研究.

研究的目的:

调查多巴胺D1和D2受体表达神经元中的m6A甲基化及其读者蛋白YTHDF1的功能.
阐明 m⁶A 在神经元适应环境挑战中的作用.

主要方法:

在D1和D2神经元中,细胞类型特定的Mettl14 (m6A甲基转移酶) 和Ythdf1 (m6A阅读器) 基因被删除.
在三个范式的行为测试.
对细胞和分子反应的分析,包括蛋白质合成和mRNA结合.

主要成果:

在D1神经元中Mettl14或Ythdf1的缺陷影响了D1依赖学习;在D2神经元中缺陷影响了D2依赖学习.
对环境刺激的细胞反应 (神经元发射) 和分子反应 (蛋白质合成) 在突变小鼠中被削弱.
YTHDF1缺陷模仿了Mettl14缺陷,表明YTHDF1是条纹体中的关键调解者.
可卡因增加了YTHDF1与编码结构蛋白的mRNA的结合,这表明它在突触可塑性中发挥了作用.

结论:

在成人多巴胺神经元中,A-YTHDF1通路对于适应性行为,细胞和分子反应至关重要.
YTHDF1调解了线条体中m6A甲基化的功能影响.
这条通路在学习和突触可塑性中起着至关重要的作用,在D1和D2神经元中具有细胞类型特定的作用.

更多相关视频

A Method for Measuring RNA N6-methyladenosine Modifications in Cells and Tissues

A Method for Measuring RNA N6-methyladenosine Modifications in Cells and Tissues

Published on: December 5, 2016

Rapid In Vivo Fixation and Isolation of Translational Complexes from Eukaryotic Cells

Rapid In Vivo Fixation and Isolation of Translational Complexes from Eukaryotic Cells

Published on: December 25, 2021

相关概念视频

Regulation of Expression at Multiple Steps

Regulation of Expression at Multiple Steps

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...

Riboswitches

Riboswitches

Riboswitches are non-coding mRNA domains that regulate the transcription and translation of downstream genes without the help of proteins. Riboswitches bind directly to a metabolite and can form unique stem-loop or hairpin structures in response to the amount of the metabolite present. They have two distinct regions – a metabolite-binding aptamer and an expression platform.
The aptamer has high specificity for a particular metabolite which allows riboswitches to specifically regulate...

Regulation of Expression Occurs at Multiple Steps

Regulation of Expression Occurs at Multiple Steps

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...

Master Transcription Regulators

Master Transcription Regulators

Master transcription regulators are regulatory proteins that are predominantly responsible for regulating the expression of multiple genes. Often these genes work in concert to drive a complex process. Activation of a master transcription regulator can lead to a cascade of transcriptional activation necessary for that outcome. These regulators can directly bind to the regulatory sequences of the various genes involved, or they can indirectly regulate transcription by binding to regulatory...

RNA Stability

RNA Stability

Intact DNA strands can be found in fossils, while scientists sometimes struggle to keep RNA intact under laboratory conditions. The structural variations between RNA and DNA underlie the differences in their stability and longevity. Because DNA is double-stranded, it is inherently more stable. The single-stranded structure of RNA is less stable but also more flexible and can form weak internal bonds. Additionally, most RNAs in the cell are relatively short, while DNA can be up to 250 million...

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...