在5'未翻译区域使用可解释的多任务学习模型发现监管动机
Weizhong Zheng1, John H C Fong1, Yuk Kei Wan1
1School of Biomedical Sciences, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, China.
Cell systems
|November 28, 2023
概括
MTtrans通过识别5'未翻译区域 (UTR) 中的保存序列动机来预测mRNA翻译率. 这种工具准确地解读了调控元素,有助于理解基因表达控制.
科学领域:
- 分子生物学分子生物学
- 基因组学就是基因组学.
- 生物信息学是一种生物信息学.
背景情况:
- 5'未翻译区域 (UTR) 的序列元素影响信使RNA (mRNA) 的翻译效率.
- 控制这些序列的准确监管语法在很大程度上是未知的.
研究的目的:
- 开发一个计算工具,MTtrans,用于根据5' UTR序列预测翻译速率.
- 识别涉及不同数据集和物种的翻译调节的保存序列动机.
主要方法:
- 开发了MTtrans,这是一个预测翻译率的多任务学习模型.
- 采用光激活细胞分类与深度测序 (FACS-seq) 结合用于实验验证.
- 引入了GRU-rewiring用于解释反复复发的神经网络隐藏状态和分析突变效应.
主要成果:
- 与现有方法相比,MTtrans显示出更高的准确性和图案可转移性.
- 确定了具有在翻译控制中重要作用的进化保守序列动图.
- GRU-rewiring成功地确定了监管元素丰富的位置,并阐明了局部突变的影响.
结论:
- MTtrans是一种有效的工具,可以在5' UTRs中解读翻译监管动机.
- 这些发现增强了我们对基因表达的基于序列的控制的理解.
- GRU-rewiring为基于序列的监管机制的可解释性提供了新的见解.
相关概念视频
Regulation of Expression at Multiple Steps
917
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...
917
Regulated 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
Regulation 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
Master Transcription Regulators
6.9K
Master transcription regulators are regulatory proteins that are predominantly responsible for regulating the expression of multiple genes. Often these genes work in concert to drive a complex process. Activation of a master transcription regulator can lead to a cascade of transcriptional activation necessary for that outcome. These regulators can directly bind to the regulatory sequences of the various genes involved, or they can indirectly regulate transcription by binding to regulatory...
6.9K
Cis-regulatory Sequences
3.0K
3.0K
Leaky Scanning
5.1K
During most eukaryotic translation processes, the small 40S ribosome subunit scans an mRNA from its 5' end until it encounters the first start AUG codon. The large 60S ribosomal subunit then joins the smaller one to initiate protein synthesis. The location of the translation initiation is largely determined by the nucleotides near the start codon as there may be multiple translation initiation sites present on the mRNA. Marilyn Kozak discovered that the sequence RCCAUGG (where R...
5.1K


