在Homo sapiens mRNA 5'UTR序列中识别潜在的 рибо开关元件,使用正无标记机器学习
William S Raymond1, Jacob DeRoo1, Brian Munsky1,2
1School of Biomedical Engineering, Colorado State University, Fort Collins, Colorado, United States of America.
PloS one
|April 24, 2025
概括
研究人员开发了机器学习分类器,以识别人类mRNA中的潜在核糖突变. 这项研究强调了436个人类5'未翻译区域 (5'UTR) 作为进一步研究新型 рибо交换机功能的候选人.
科学领域:
- 分子生物学分子生物学
- 生物信息学是一种生物信息学.
- 基因组学就是基因组学.
背景情况:
- 带状切换器是各种生物体中发现的调节性RNA元素,通过结合子来控制基因表达.
- 虽然在细菌和其他真核生物中很常见,但纯RNA小分子核糖开关在人类 (智人) 中尚未确定.
- 最近的发现表明,在人类的转化体中可能存在类似于 рибо开关的机制,需要进一步研究.
研究的目的:
- 在人类mRNA5'未翻译区域 (5'UTRs) 中计算识别潜在的小分子依赖的核糖开关.
- 开发和应用机器学习模型来选人类5'UTRs的大数据集以检测 рибо开关活动.
- 为未来的实验验证提供候选人类5'UTR的排名数据库.
主要方法:
- 使用一种正的未标记的学习方法,使用机器学习分类器,这些分类器在RNAcentral的已知 рибо交换机序列上训练.
- 应用了20个不同的分类器,包括序列和次要结构特征,对来自UTRdb.com的48,031个人类5'UTR序列进行分类.
- 进行交叉验证以评估分类器的准确性,达到75%-99%的范围.
主要成果:
- 通过至少一个分类器,确定了1533个人类5'UTR序列作为潜在的 рибо开关.
- 确定了436个人类5'UTR,由所有20个分类器一致标记为潜在的 рибо交换机候选者.
- 将这些候选序列映射到已知的 рибо开关中,以推断潜在的连接体相互作用和功能.
结论:
- 这项研究提出了一个计算框架,用于发现人类基因组中的新型核突变器.
- 确定了一组重要的436个人类5'UTRs作为高可信度候选人,可以容纳功能性核糖突变器.
- 提供的数据库是试验人员的宝贵资源,旨在发现人类特定的核糖转换机制.
相关概念视频
Riboswitches
8.0K
Riboswitches are non-coding mRNA domains that regulate the transcription and translation of downstream genes without the help of proteins. Riboswitches bind directly to a metabolite and can form unique stem-loop or hairpin structures in response to the amount of the metabolite present. They have two distinct regions – a metabolite-binding aptamer and an expression platform.
The aptamer has high specificity for a particular metabolite which allows riboswitches to specifically regulate...
The aptamer has high specificity for a particular metabolite which allows riboswitches to specifically regulate...
8.0K
Ribosome Profiling
3.4K
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...
3.4K
Types of RNA
62.6K
Overview
Three main types of RNA are involved in protein synthesis: messenger RNA (mRNA), transfer RNA (tRNA), and ribosomal RNA (rRNA). These RNAs perform diverse functions and can be broadly classified as protein-coding or non-coding RNA. Non-coding RNAs play important roles in the regulation of gene expression in response to developmental and environmental changes. Non-coding RNAs in prokaryotes can be manipulated to develop more effective antibacterial drugs for human or animal use.
RNA...
Three main types of RNA are involved in protein synthesis: messenger RNA (mRNA), transfer RNA (tRNA), and ribosomal RNA (rRNA). These RNAs perform diverse functions and can be broadly classified as protein-coding or non-coding RNA. Non-coding RNAs play important roles in the regulation of gene expression in response to developmental and environmental changes. Non-coding RNAs in prokaryotes can be manipulated to develop more effective antibacterial drugs for human or animal use.
RNA...
62.6K
Leaky Scanning
5.0K
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...
5.0K
Improving Translational Accuracy
8.5K
Base complementarity between the three base pairs of mRNA codon and the tRNA anticodon is not a failsafe mechanism. Inaccuracies can range from a single mismatch to no correct base pairing at all. The free energy difference between the correct and nearly correct base pairs can be as small as 3 kcal/ mol. With complementarity being the only proofreading step, the estimated error frequency would be one wrong amino acid in every 100 amino acids incorporated. However, error frequencies observed in...
8.5K
Regulated mRNA Transport
6.2K
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...
6.2K


