使用TCGA乳腺癌转录数据对长非编码RNA对全球基因表达变异的调控影响的定量估计
Xiaoman Xie1, Saurabh Sinha2,3
1Center for Biophysics and Quantitative Biology, University of Illinois Urbana-Champaign, Urbana, Illinois, United States of America.
PLoS computational biology
|June 5, 2024
概括
长非编码RNAs (lncRNAs) 在乳腺癌中显著调节基因表达,解释了16%的基因中20%以上的变异. 交叉作用的 lncRNA 显示出比交叉作用的 lncRNA 具有更大的调节影响.
科学领域:
- 基因组学和系统生物学
- 分子生物学分子生物学
- 癌症研究 癌症研究
背景情况:
- 长非编码RNAs (lncRNAs) 越来越多地被认为是它们在生物过程中的调节作用,包括癌症.
- 尽管取得了进展,但关于lncRNAs的机制和全球目标仍然存在重大知识差距.
- 了解lncRNA介导的基因表达控制的程度对于破译复杂的生物系统至关重要.
研究的目的:
- 量化归因于乳腺癌中lncRNA调节的基因表达变异的比例.
- 研究 lncRNA 位置 (cis vs. trans) 对监管影响的影响.
- 构建一个高可靠性 lncRNA基因调控网络,结合机械洞察力.
主要方法:
- 来自乳腺癌患者队列的RNA测序数据的分析.
- 应用回归模型来解释基因表达变异,使用选择的lncRNA调节器,考虑转录因子 (TF) 混效应.
- 定量化cis-和trans-acting lncRNA的调节影响.
- 鉴定lncRNA-蛋白相互作用及其对调节效应的影响.
- 基于共表达和机械学证据构建一个lncRNA基因调节网络.
主要成果:
- lncRNAs解释了分析的16%基因的20%以上的表达变异.
- 发现大量 (25-50%) 的调节性 lncRNAs 位于 cis 与它们的目标基因之间.
- 与转位 lncRNA 相比,cis-located lncRNAs 的全球监管影响显著更大.
- 鉴定了 lncRNA 调节效应通过特定 TFs 或 RNA 结合蛋白的存在来调节的实例.
- 开发了一种高可靠性 lncRNA基因调控网络,集成协同表达和机械数据.
结论:
- lncRNAs在推动乳腺癌的基因表达变异中发挥着重要作用,特别是那些在cis中起作用的基因表达变异.
- 本研究提供了对lncRNA调节影响的定量评估,并推动了lncRNA调节网络的重建.
- 这些发现凸显了考虑lncRNA位置和相互作用对于全面了解基因调节的重要性.
相关概念视频
02:39lncRNA - Long Non-coding RNAs
8.6K
In humans, more than 80% of the genome gets transcribed. However, only around 2% of the genome codes for proteins. The remaining part produces non-coding RNAs which includes ribosomal RNAs, transfer RNAs, telomerase RNAs, and regulatory RNAs, among other types. A large number of regulatory non-coding RNAs have been classified into two groups depending upon their length – small non-coding RNAs, such as microRNA, which are less than 200 nucleotides in length, and long non-coding RNA...
8.6K
01:23Regulation of Expression at Multiple Steps
889
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...
889
02:24Regulation 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
02:02Cis-regulatory Sequences
9.8K
Cis-regulatory sequences are short fragments of non-coding DNA that are present on the same chromosomes as the genes that they regulate. These fragments serve as binding sites for transcriptional regulators, proteins that are responsible for controlling gene transcription and differential gene expression across cell types in eukaryotes. Cis-regulatory sequences can be close to the gene of interest or thousands of bases away in the DNA sequence; however, those sequences that are further away are...
9.8K
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
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