由低氧驱动的EXOSC10脱SUMOylation促进了转录组形状的适应性变化
Chrysa Filippopoulou1, Chairini C Thomé2, Sofia Perdikari3
1Laboratory of Biochemistry, Faculty of Medicine, University of Thessaly, Biopolis, 41500, Larissa, Greece.
Cellular and molecular life sciences : CMLS
|January 26, 2024
概括
低氧降低了外基因组子单位10 (EXOSC10) 的SUMOylation,这是一个RNA外基因组酶,独立于HIF. 这种EXOSC10SUMOylation和局部化的动态调节有助于细胞适应低氧条件.
科学领域:
- 细胞生物学 细胞生物学
- 分子生物学分子生物学
- 生物化学 生物化学
背景情况:
- 缺氧会触发适应性细胞反应,主要是通过依赖HIF的转录.
- 包括翻译后修改在内的转录独立机制至关重要,但不太了解.
- 蛋白质SUMOylation在低氧适应中的作用需要进一步研究.
研究的目的:
- 研究蛋白质SUMOylation在细胞适应低氧的过程中的作用.
- 确定负责SUMOylation和Exosome子单元10 (EXOSC10) 的脱SUMOylation的酶.
- 在低氧条件下阐明EXOSC10 SUMOylation变化的功能后果.
主要方法:
- 研究的蛋白质SUMOylation在对缺氧的反应中发生变化.
- 确定USP36作为SUMOylating酶和SENP3作为EXOSC10的deSUMOylating酶.
- 在低氧条件下分析了EXOSC10局部化及其对RNA处理和基因表达的影响.
主要成果:
- 缺氧显著降低EXOSC10 SUMOylation在一个HIF独立的方式.
- 在deSUMOylation过程中,EXOSC10从USP36中解离,并从细胞核转移到细胞核.
- 改变的EXOSC10 SUMOylation会影响mRNA转录组,影响与缺氧相关的基因表达.
结论:
- 动态调节EXOSC10 SUMOylation和核细胞-核质局部化是对低氧的关键转录独立适应性反应.
- 这种规则微调RNA降解机制,以促进细胞适应低氧.
- 研究结果揭示了一种新的机制,可以控制缺氧期间的基因表达.
相关概念视频
01:36What is Gene Expression?
8.5K
A gene is a stretch of DNA that serves as the blueprint for functional RNAs and proteins. Since DNA is comprised of nucleotides and proteins are comprised of amino acids, a mediator is required to convert the information encoded in DNA into proteins. This mediator is the messenger RNA (mRNA). mRNA copies the blueprint from DNA by a process called transcription. In eukaryotes, transcription occurs in the nucleus by complementary base-pairing with the DNA template. The mRNA is then...
8.5K
02:32Exon Recombination
3.6K
The evolution of new genes is critical for speciation. Exon recombination, also known as exon shuffling or domain shuffling, is an important means of new gene formation. It is observed across vertebrates, invertebrates, and in some plants such as potatoes and sunflowers. During exon recombination, exons from the same or different genes recombine and produce new exon-intron combinations, which might evolve into new genes.
Exon shuffling follows “splice frame rules.” Each exon...
Exon shuffling follows “splice frame rules.” Each exon...
3.6K
02:24Ribosome Profiling
3.5K
Ribosome profiling or ribo-sequencing is a deep sequencing technique that produces a snapshot of active translation in a cell. It selectively sequences the mRNAs protected by ribosomes to get an insight into a cell’s translation landscape at any given point in time.
Applications of ribosome profiling
Ribosome profiling has many applications, including in vivo monitoring of translation inside a particular organ or tissue type and quantifying new protein synthesis levels.
The technique...
Applications of ribosome profiling
Ribosome profiling has many applications, including in vivo monitoring of translation inside a particular organ or tissue type and quantifying new protein synthesis levels.
The technique...
3.5K
01:22MicroRNAs
3.0K
MicroRNA (miRNA) are short, regulatory RNA transcribed from introns (non-coding regions of a gene) or intergenic regions (stretches of DNA present between genes). Several processing steps are required to form biologically active, mature miRNA. The initial transcript, called primary miRNA (pri-mRNA), base-pairs with itself, forming a stem-loop structure. Within the nucleus, an endonuclease enzyme, called Drosha, shortens the stem-loop structure into hairpin-shaped pre-miRNA. After the pre-miRNA...
3.0K
01:33Pleiotropy
40.5K
Pleiotropy is the phenomenon in which a single gene impacts multiple, seemingly unrelated phenotypic traits. For example, defects in the SOX10 gene cause Waardenburg Syndrome Type 4, or WS4, which can cause defects in pigmentation, hearing impairments, and an absence of intestinal contractions necessary for elimination. This diversity of phenotypes results from the expression pattern of SOX10 in early embryonic and fetal development. SOX10 is found in neural crest cells that form melanocytes,...
40.5K
02:51mRNA 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