剖析了指导m6A沉积和演变的序列和结构决定因素,通过物种间和物种内杂交
Ran Shachar1, David Dierks1, Miguel Angel Garcia-Campos1
1Department of Molecular Genetics, Weizmann Institute of Science, Rehovot, 7630031, Israel.
Genome biology
|February 15, 2024
概括
RNA甲基化 (m6A) 变异性主要是由影响RNA结构和共识动机的遗传序列变化驱动的. 这些cis作用变异影响基因表达水平,揭示了m6A进化的关键决定因素.
科学领域:
- 分子生物学分子生物学
- 遗传学 遗传学 是一个
- 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:
- N6-甲基氨酸 (m6A) 是最常见的mRNA修饰,调节mRNA稳定性.
- 在物种之间和物种内部的m6A分布中存在显著的变异性.
- 遗传序列 (cis) 与细胞环境 (trans) 对这种变异性的相对贡献仍然不清楚.
研究的目的:
- 调查RNA甲基化 (m6A) 变化的潜在机制和决定因素.
- 区分 cis 作用的基因变异和 trans 作用因子在 m6A 分布中的作用.
- 了解m6A变异性对基因表达的功能影响.
主要方法:
- 在酵母和哺乳动物系统中对物种间和物种内杂交的分析.
- 应用大规模并行报告测定 (MPRAs).
- 重新分析m6A定量特征位置 (m6A-QTL) 数据.
主要成果:
- m6A的进化和变异性主要是由cis作用的遗传变异驱动的.
- 确定了两个关键机制:m6A共识动机的改变和mRNA二次结构的变化.
- 影响RNA结构的突变,即使是离基因远的突变,也会因果影响m6A水平.
- 一个等位基因特定的m6A差异与一个等位基因特定的基因表达变化相关.
结论:
- 遗传序列变异是m6A进化和多样性的主要驱动因素.
- 无论是m6A动机序列还是mRNA结构变异,都决定了甲基化模式.
- m6A水平的变化直接影响等位基因特异性基因表达调节.
相关概念视频
02:29Hybrid Zones
17.0K
Hybrid zones are narrow regions where two closely related species interact, mate, and produce hybrids. Relative to either parent species, hybrids may possess distinct phenotypic or genetic differences that impact their survival and reproductive success. The genetic variances introduced by hybridization influence species diversity and speciation processes within the hybrid zone.
17.0K
02:02Cis-regulatory Sequences
9.9K
Cis-regulatory sequences are short fragments of non-coding DNA that are present on the same chromosomes as the genes that they regulate. These fragments serve as binding sites for transcriptional regulators, proteins that are responsible for controlling gene transcription and differential gene expression across cell types in eukaryotes. Cis-regulatory sequences can be close to the gene of interest or thousands of bases away in the DNA sequence; however, those sequences that are further away are...
9.9K
02:51Multi-species Conserved Sequences
3.9K
Next-generation sequencing technologies have created large genomic databases of a variety of animals and plants. Ever since the human genome project was completed, scientists studied the genome of primates, mammals, and other phylogenetically distant living beings. Such large-scale studies have provided new insights into the evolutionary relationship between organisms.
Although the genome of each species varies greatly from each other, a few sequences are highly conserved. Such conserved...
Although the genome of each species varies greatly from each other, a few sequences are highly conserved. Such conserved...
3.9K
02:32Position-effect Variegation
6.3K
In 1928, a German botanist Emil Heitz observed the moss nuclei with a DNA binding dye. He observed that while some chromatin regions decondense and spread out in the interphase nucleus, others do not. He termed them euchromatin and heterochromatin, respectively. He proposed that the heterochromatin regions reflect a functionally inactive state of the genome. It was later confirmed that heterochromatin is transcriptionally repressed, and euchromatin is transcriptionally active chromatin.
6.3K
01:17What is a Species?
44.1K
Overview
44.1K
01:20Mismatch Repair
4.8K
Organisms are capable of detecting and fixing nucleotide mismatches that occur during DNA replication. This sophisticated process requires identifying the new strand and replacing the erroneous bases with correct nucleotides. Mismatch repair is coordinated by many proteins in both prokaryotes and eukaryotes.
The Mutator Protein Family Plays a Key Role in DNA Mismatch Repair
The human genome has more than 3 billion base pairs of DNA per cell. Prior to cell division, that vast amount of genetic...
The Mutator Protein Family Plays a Key Role in DNA Mismatch Repair
The human genome has more than 3 billion base pairs of DNA per cell. Prior to cell division, that vast amount of genetic...
4.8K