在斑马鱼胚胎发生过程中,细胞类型特定的mRNA转录和降解动力学来自代谢标记的单细胞RNA-seqq
Lior Fishman1, Avani Modak2, Gal Nechooshtan1
1Department of Genetics, Silberman Institute of Life Sciences, The Hebrew University of Jerusalem, Edmond J. Safra Campus, Jerusalem, 9190401, Israel.
Nature communications
|April 10, 2024
概括
这项研究量化了斑马鱼胚胎发育中的mRNA转录和降解率. 它揭示了细胞类型特定的mRNA调节,影响胚胎发育期间的基因表达.
科学领域:
- 发展生物学 发展生物学
- 分子生物学分子生物学
- 基因组学就是基因组学.
背景情况:
- 多能细胞在胚胎发育过程中通过改变基因表达来分化为专门的细胞类型.
- 了解mRNA转录和降解的动态对于破译发育胚胎中的基因表达特征至关重要.
研究的目的:
- 在斑马鱼胚胎发育过程中,系统量化单个细胞类型的mRNA转录和降解率.
- 调查这些速率如何帮助塑造细胞类型特定的基因表达特征.
主要方法:
- 结合单细胞RNA测序 (scRNA-Seq) 与代谢标记,以区分新转录的 (雌激素) 和先前存在的 (母体) mRNA.
- 开发了动力模型来计算单细胞水平的mRNA转录和降解速率.
主要成果:
- 揭示了数千个基因和细胞类型的mRNA转录和降解率的显著变化.
- 确定了许多转录物的转录和降解的协调调节.
- 与不同mRNA降解速率相关的序列元素.
- 发现了母体转录在原始生殖细胞和包裹层细胞中的选择性保留.
结论:
- 这项研究为分析动态胚胎发育过程中的mRNA调节提供了定量框架.
- 强调转录和降解在建立细胞类型特定的转录组中的重要性.
- 提供了对早期细胞命运决定背后的机制的见解.
相关概念视频
02:01pre-mRNA Processing
In eukaryotic cells, transcripts made by RNA polymerase are modified and processed before exiting the nucleus. Unprocessed RNA is called precursor mRNA or pre-mRNA to distinguish it from mature mRNA.
Once about 20-40 ribonucleotides have been joined together by RNA polymerase, a group of enzymes adds a “cap” to the 5’ end of the growing transcript. In this process, a 5’ phosphate is replaced by modified guanosine that has a methyl group attached to it (7-Methyl guanosine). This 5’ cap helps the...
Once about 20-40 ribonucleotides have been joined together by RNA polymerase, a group of enzymes adds a “cap” to the 5’ end of the growing transcript. In this process, a 5’ phosphate is replaced by modified guanosine that has a methyl group attached to it (7-Methyl guanosine). This 5’ cap helps the...
02:31Nuclear Export of mRNA
Before mRNAs are exported to the cytoplasm, it is crucial to check each mRNA for structural and functional integrity. Eukaryotic cells use several different mechanisms, collectively known as mRNA surveillance, to look for irregularities in mRNAs. Irregular or aberrant mRNA are rapidly degraded by various enzymes. If a defective mRNA escapes the surveillance, it would be translated into a protein which would either be non-functional or not function properly. One of the primary irregularities in...
02:27Nonsense-mediated mRNA Decay
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,...
02:51mRNA Stability and Gene Expression
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
01:35Pre-mRNA Processing: Modification of pre-mRNA Ends
In eukaryotic cells, transcripts made by RNA polymerase are modified and processed before exiting the nucleus. Unprocessed RNA is called precursor mRNA or pre-mRNA to distinguish it from mature mRNA.
Once about 20-40 ribonucleotides have been joined together by RNA polymerase, a group of enzymes adds a cap to the 5' end of the growing transcript. In this process, a 5' phosphate is replaced by modified guanosine that has a methyl group attached (7-methyl guanosine). This 5' cap helps the cell...
Once about 20-40 ribonucleotides have been joined together by RNA polymerase, a group of enzymes adds a cap to the 5' end of the growing transcript. In this process, a 5' phosphate is replaced by modified guanosine that has a methyl group attached (7-methyl guanosine). This 5' cap helps the cell...
01:23Regulation 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 addition of a...