综合模型定义了Nova拼接监管网络及其组合控制
Chaolin Zhang1, Maria A Frias, Aldo Mele
1Laboratory of Molecular Neuro-Oncology, Howard Hughes Medical Institute, The Rockefeller University, 1230 York Avenue, New York, NY 10021, USA. czhang@rockefeller.edu
概括
研究人员开发了一种贝叶斯网络方法来绘制RNA调节网络的地图. 这种方法确定了大约700个由小鼠大脑中的Nova因子调节的RNA替代拼接事件,揭示了复杂的调节相互作用.
科学领域:
- 分子生物学分子生物学
- 基因组学就是基因组学.
- 神经科学是一个神经科学.
背景情况:
- 对于生物多样性来说,RNA替代拼接至关重要,但全面的监管网络仍未定义.
- 现有的全基因组技术在定义可靠的RNA调节网络方面存在局限性.
研究的目的:
- 为了解哺乳动物RNA调节,制定一个一般的系统层面的方法.
- 在小鼠大脑中识别神经元特异性拼接因子Nova的直接目标和调节网络.
主要方法:
- 利用贝叶斯网络来概率地建模各种数据集,整合RNA结合,拼接微阵列,Nova结合动机和进化数据.
- 应用了这种整合策略来预测Nova监管机构的目标网络.
主要成果:
- 确定了大约700个由Nova在小鼠大脑中直接调节的替代拼接事件.
- 揭示了涉及Nova和Fox拼接因子的组合调节.
- 发现了酸化和拼接之间的相互作用,与神经系统疾病的潜在联系.
结论:
- 开发了一种可通用的计算方法,用于在系统层面绘制RNA调节网络.
- 这项研究提供了关于哺乳动物大脑RNA调节的复杂性的见解.
- 研究结果表明,RNA拼接失调和神经系统疾病之间存在潜在的联系.
相关概念视频
Combinatorial Gene Control
Combinatorial gene control is the synergistic action of several transcriptional factors to regulate the expression of a single gene. The absence of one or more of these factors may lead to a significant difference in the level of gene expression or repression.
The expression of more than 30,000 genes is controlled by approximately 2000-3000 transcription factors. This is possible because a single transcription factor can recognize more than one regulatory sequence. The specificity in gene...
The expression of more than 30,000 genes is controlled by approximately 2000-3000 transcription factors. This is possible because a single transcription factor can recognize more than one regulatory sequence. The specificity in gene...
Regulation 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...
Regulation of Expression Occurs at Multiple Steps
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...
Regulation of Expression Occurs at Multiple Steps
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...
Interactions Between Signaling Pathways
Signaling cascades usually lack linearity. Multiple pathways interact and regulate one another, allowing cells to integrate and respond to diverse environmental stimuli.
Convergence and divergence, and cross-talk between signaling pathways
Two distinct signaling pathways can converge on a single functional unit, which may either be a single protein or a complex of proteins. The response is either functionally distinct or synergistic between the two pathways but different from the response...
Convergence and divergence, and cross-talk between signaling pathways
Two distinct signaling pathways can converge on a single functional unit, which may either be a single protein or a complex of proteins. The response is either functionally distinct or synergistic between the two pathways but different from the response...
Cooperative Binding of Transcription Regulators
Transcriptional regulators bind to specific cis-regulatory sequences in the DNA to regulate gene transcription. These cis-regulatory sequences are very short, usually less than ten nucleotide pairs in length. The short length means that there is a high probability of the exact same sequence randomly occurring throughout the genome. Since regulators can also bind to groups of similar sequences, this further increases the chances of random binding. Transcriptional regulators form dimers that...

