通过单细胞RNA测序对心脏非编码转录组的评估确定了FIXER,一种保存的长型非编码RNA
Parisa Aghagolzadeh1, Isabelle Plaisance1, Riccardo Bernasconi1
1Experimental Cardiology Unit, Division of Cardiology, Department of Cardiovascular Medicine, University of Lausanne Medical School, Switzerland (P.A., I.P., R.B., M.N., T.P.).
Circulation
|July 10, 2023
概括
研究人员发现了一种新的长非编码RNA,FIXER, 静止FIXER可以抑制纤维化,改善心脏病发作后的心脏功能,为心脏病提供新的治疗点.
科学领域:
- 心血管生物学
- 分子心脏病学
- 基因组学
背景情况:
- 心脏纤维细胞在受损的心脏组织中分化为肌纤维细胞,导致纤维化和功能障碍.
- 肌纤维细胞是治疗点,但缺乏特定的标志物阻碍了治疗的发展.
- 长非编码RNAs (lncRNAs) 是细胞特异性的,对心血管功能至关重要.
研究的目的:
- 评估 lncRNA转录组在单细胞RNA测序中的潜力,以识别心脏细胞亚群.
- 发现针对心脏病治疗的新型细分群体标志物.
主要方法:
- 在心脏非肌细胞中进行深度单细胞RNA测序.
- 在纤维细胞和肌纤维细胞群中识别异质性的 lncRNA转录组.
- 候选 lncRNA 的选择和功能验证,FIXER.
主要成果:
- 在单细胞研究中,可以单独通过 lncRNA 表达来确定心脏细胞的身份.
- 在肌纤维细胞亚群中特定丰富的 lncRNAs.
- 抑制lncRNA FIXER (纤维化LOX- locus增强酶RNA) 减少了心脏纤维化,并改善了心脏病发作后的功能.
- FIXER与CBX4相互作用以调节RUNX1的表达,控制纤维化基因程序.
结论:
- lncRNA表达足以界定哺乳动物心脏中的细胞类型.
- 在肌纤维细胞中鉴定出独特的 lncRNA,FIXER 是心脏纤维化治疗的有希望的点.
- 在人体中,FIXER的活性保持不变,这表明它在治疗心脏病方面具有转化潜力.
相关概念视频
02:18Alternative RNA Splicing
Alternative RNA splicing is the regulated splicing of exons and introns to produce different mature mRNAs from a single pre-mRNA. Unlike in constitutive splicing where a single gene produces a single type of mRNA, alternative splicing allows an organism to produce multiple proteins from a single gene and plays an important role in protein diversity.
There are five types of alternative RNA splicing that vary in the ways the pre-mRNA segments are removed or retained in the mature mRNA. The first...
There are five types of alternative RNA splicing that vary in the ways the pre-mRNA segments are removed or retained in the mature mRNA. The first...
02:39lncRNA - Long Non-coding RNAs
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 (lncRNA)...
02:24Ribosome Profiling
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 helps...
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 helps...
01:20Types of 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 regulating 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 Performs Diverse...
RNA Performs Diverse...
02:18Alternative RNA Splicing
Alternative RNA splicing is the regulated splicing of exons and introns to produce different mature mRNAs from a single pre-mRNA. Unlike in constitutive splicing where a single gene produces a single type of mRNA, alternative splicing allows an organism to produce multiple proteins from a single gene and plays an important role in protein diversity.
There are five types of alternative RNA splicing that vary in the ways the pre-mRNA segments are removed or retained in the mature mRNA. The first...
There are five types of alternative RNA splicing that vary in the ways the pre-mRNA segments are removed or retained in the mature mRNA. The first...
02:39lncRNA - Long Non-coding RNAs
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 (lncRNA)...