人类RNA基酶DDX3X和DDX3Y的转录后交叉和自我调节缓冲表达
Shruthi Rengarajan1,2, Jason Derks3, Daniel W Bellott1
1Whitehead Institute, Cambridge, MA 02142, USA.
bioRxiv : the preprint server for biology
|July 19, 2024
概括
DDX3X和DDX3Y基因表现出剂量敏感性,并通过负反循环进行调节. 这种交叉调节缓冲蛋白质水平,表明自体调节的进化适应.
科学领域:
- 遗传学 是一个遗传学.
- 分子生物学分子生物学
- 进化生物学 进化生物学
背景情况:
- DDX3X基因编码了一个关键的RNA螺旋酶,它与发育障碍和癌症有关.
- DDX3X及其与Y结合的同类DDX3Y是自体基因的残余,这些基因在性染色体进化过程中幸存下来.
- 在具有Y同类的X链基因中,DDX3X对剂量特别敏感.
研究的目的:
- 研究DDX3X和DDX3Y的剂量敏感性和调节机制.
- 了解这些基因是如何调节的,以应对性染色体数量的变化.
- 探索基因调节的进化过渡从自体到性染色体.
主要方法:
- 对具有性染色体无倍化 (例如,XXY,XXX) 的细胞进行分析.
- 在46,XY细胞中进行基因敲除的CRISPR干扰 (CRISPRi).
- 在46,XX细胞中化学抑制DDX3X蛋白活性.
- 对新转录的RNA进行代谢标记,以研究mRNA的稳定性.
主要成果:
- 增加的Y染色体数导致DDX3X转录水平降低,增加的X染色体数导致DDX3Y转录水平降低.
- 在46,XY细胞中,DDX3X或DDX3Y的淘汰会增加同源基因的转录水平.
- 在46,XX细胞中抑制DDX3X蛋白活性增加了DDX3X转录水平.
- 观察到DDX3X和DDX3Y之间的负交叉调节 (在XY细胞中) 和DDX3X的负自调节 (在XX细胞中).
- 调节通过mRNA不稳定发生,缓冲总DDX3X和DDX3Y蛋白水平.
结论:
- 通过负自动和交叉调节机制,DDX3X和DDX3Y表达受到严格监管.
- 这些调节系统缓冲蛋白质水平,代表了祖先自体基因调节的进化适应.
- 这些发现揭示了性别染色体上基因调节的演变.
相关概念视频
Chromatin Structure Regulates pre-mRNA Processing
7.0K
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...
7.0K
Regulation of Expression at Multiple Steps
886
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...
886
Regulation of Expression Occurs at Multiple Steps
22.6K
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...
22.6K
Dosage Compensation
6.1K
In animals, gender is determined by the number and type of sex chromosome. For example, human females have two X chromosomes, and males have one X and one Y chromosome, whereas C.elegans with one X chromosome is a male, and the one with two X chromosomes is a hermaphrodite.
In addition to sexual development, the X chromosome has genes involved in autosomal functions such as brain development and the immune system. Therefore, males and females with distinct numbers of X chromosomes will...
In addition to sexual development, the X chromosome has genes involved in autosomal functions such as brain development and the immune system. Therefore, males and females with distinct numbers of X chromosomes will...
6.1K
Exon 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
RNA Stability
33.5K
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...
33.5K


