引子-引子边界抑制了m6A沉积,使得m6A分布的标志,更长的mRNA半衰期和灵活的蛋白质编码成为可能
Zhiyuan Luo1, Qilian Ma2, Shan Sun2
1The Jackson Laboratory, Bar Harbor, ME, 04609, USA.
Nature communications
|July 13, 2023
概括
外子-内子边界影响N6-甲基氨酸 (m6A) mRNA的修饰,抑制了结合点附近的沉积. 这种调节有助于mRNA稳定性和灵活的蛋白质编码,其中外因子结合复合体发挥了部分作用.
科学领域:
- 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.
- 生物信息学是一种生物信息学.
背景情况:
- N6-甲基氨酸 (m6A) 是一个关键的mRNA修饰.
- 在m6A沉积中的区域偏差表明了监管机制.
- 外子-内子边界对m6A的影响尚不清楚.
研究的目的:
- 为了研究外子-内子边界对m6A沉积的影响.
- 为了确定m6A压缩在拼接部位附近的程度.
- 探索这一法规对mRNA稳定性的功能影响.
主要方法:
- 深度学习建模用于预测m6A沉积.
- 对m6A信号变化的实验验证.
- 对m6A增强器和消声器的分析.
- 对埃克森交汇综合体 (EJC) 参与的评估.
主要成果:
- 外子-内子边界抑制了12%至34%的m6A沉积在相邻的外子中.
- m6A信号在未连接的转录中增加.
- 抑制的m6A位点呈现出不同的增强器/沉默器配置.
- m6A对多外显子mRNA的稳定性有显著的贡献.
- 在短时间的内部测试中,EJC显示了对抑制的部分贡献.
结论:
- 外子-内子边界作为m6A沉积的调节元素.
- 这一规定影响了mRNA稳定性和蛋白质编码灵活性.
- 除了EJC之外的其他因素还会影响外子-内子边界m6A的抑制.
相关概念视频
Chromatin Structure Regulates pre-mRNA Processing
7.1K
In eukaryotic cells, nascent mRNA transcripts need to undergo many post-transcriptional modifications to reach the cell cytoplasm and translate into functional proteins. For a long time, transcription and pre-mRNA processing were considered two independent events that occur sequentially in the cell. However, it has now been well established that transcription and pre-mRNA processing are two simultaneous processes that are precisely regulated inside the cell.
The chromatin structure, especially...
The chromatin structure, especially...
7.1K
Alternative RNA Splicing
21.4K
Alternative RNA splicing is the regulated splicing of exons and introns to produce different mature mRNAs from a single pre-mRNA. Unlike in constitutive splicing where a single gene produces a single type of mRNA, alternative splicing allows an organism to produce multiple proteins from a single gene and plays an important role in protein diversity.
There are five types of alternative RNA splicing that vary in the ways the pre-mRNA segments are removed or retained in the mature mRNA. The first...
There are five types of alternative RNA splicing that vary in the ways the pre-mRNA segments are removed or retained in the mature mRNA. The first...
21.4K
RNA Stability
33.7K
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...
33.7K
mRNA Stability and Gene Expression
5.6K
The structure and stability of mRNA molecules regulates gene expression, as mRNAs are a key step in the pathway from gene to protein. In eukaryotes, the half-life of mRNA varies from a few minutes up to several days. mRNA stability is essential in growth and development. The absence of the proteins regulating its stability, such as tristetraprolin in mice, can cause systemic issues, including bone marrow overgrowth, inflammation, and autoimmunity.
Cis-acting Elements involved in mRNA stability
Cis-acting Elements involved in mRNA stability
5.6K
Nonsense-mediated mRNA Decay
10.7K
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,...
10.7K
RNA Splicing
56.5K
Splicing is the process by which eukaryotic RNA is edited before its translation into protein. The RNA strand transcribed from eukaryotic DNA is called the primary transcript. The primary transcripts that become mRNAs are called precursor messenger RNAs (pre-mRNAs). Eukaryotic pre-mRNA contains alternating sequences of exons and introns. Exons are nucleotide sequences that code for proteins, whereas introns are the non-coding regions. In RNA splicing, introns are removed and exons are bonded...
56.5K


