控制脊椎动物卵细胞和早期胚胎中的多甲尾长度和翻译
Kehui Xiang1, Jimmy Ly2, David P Bartel1
1Howard Hughes Medical Institute, Cambridge, MA 02142, USA; Whitehead Institute for Biomedical Research, Cambridge, MA 02142, USA; Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
Developmental cell
|March 9, 2024
概括
研究人员发现,一个短的UUUUA元素,与PAS一起,在早期发育过程中控制mRNA多化. 这一发现澄清了mRNA尾巴长度的变化如何在卵细胞和胚胎中协调基因表达.
科学领域:
- 分子生物学分子生物学
- 发展生物学 发展生物学
- 遗传学 是一个遗传学.
背景情况:
- 在卵细胞成熟和早期胚胎发生过程中,mRNA多A尾长动态对于调节基因表达至关重要.
- 控制这些多A尾长度变化的精确机制,特别是细胞质多基化,在很大程度上仍未被定义.
研究的目的:
- 阐明早期发育过程中调控mRNA多元A尾长动态的调控元素和机制.
- 确定特定的序列元素和情境特征,这些特征控制了细胞质多化和死化.
主要方法:
- 利用了大规模的mRNA记者库,拥有数百万个3' UTR序列变异.
- 在青卵细胞和胚胎以及鱼类胚胎中进行尾巴长度和转化概况.
- 研究了UUUUA和多基化信号 (PAS) 等特定序列元素在调节多A尾长度中的作用.
主要成果:
- 确定了UUUUA元素,与PAS结合,作为细胞质多化的一个关键决定因素,挑战了以往专注于更长的细胞质多化元素 (CPE) 的模型.
- 发现了调节UUUUA和PAS元素活动的上下文特征.
- 在卵细胞中观察到不同的调节策略 (全局死化,尾长独立的抑制) 与胚胎 (允许的多化,特定阶段的死化) 相比.
结论:
- 根据上下文特征调节的UUUUA元素和PAS,为早期青和鱼类发育中观察到的mRNA多A尾长变化提供了全面的解释.
- 这些发现揭示了跨物种mRNA调节的保存机制,对人类和小鼠的发育有影响.
- 这项工作显著提高了我们对生命早期关键阶段的转录后基因调节的理解.
相关概念视频
01:23Regulation of Expression at Multiple Steps
906
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...
906
02:24Regulation of Expression Occurs at Multiple Steps
22.7K
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...
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...
22.7K
02:22Regulated mRNA Transport
6.3K
In eukaryotes, transcription and translation are compartmentalized; an mRNA is first synthesized in the nucleus and then selectively transported to the cytoplasm for protein synthesis. Before transport, a pre-mRNA undergoes several steps of post-transcriptional modifications including splicing, 5' capping, and the addition of a poly-adenine tail. Various proteins bind to the pre-mRNA during these modifications. The mRNA transport takes place with the help of multiple proteins playing...
6.3K
01:35Pre-mRNA Processing: Modification of pre-mRNA Ends
9.3K
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...
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...
9.3K
02:01pre-mRNA Processing
52.9K
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...
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...
52.9K
02:02Meiosis II
45.6K
Meiosis II entails cell division and segregation of the sister chromatids, resulting in the production of four unique haploid gametes. The steps for meiosis II are similar to mitosis, except that meiosis II occurs in haploid cells, whereas mitosis occurs in diploid cells.
The timing and cell division patterns of meiosis differ between males and females. In male meiosis, the centrosomes are part of the formation of the meiotic spindle. However, in oocytes, including that of humans, Drosophila,...
The timing and cell division patterns of meiosis differ between males and females. In male meiosis, the centrosomes are part of the formation of the meiotic spindle. However, in oocytes, including that of humans, Drosophila,...
45.6K