特定于心肌细胞的长非编码RNA 调节心脏中的三基因的替代拼接
Yuanbiao Zhao1, Andrew S Riching1,2,3, Walter E Knight1,2,3
1Division of Cardiology, Department of Medicine (Y.Z., A.S.R., W.E.K., C.C., Y.D., A.V.A., L.A.W., K.C.W., M.R.B., P.M.B., K.S.), University of Colorado Anschutz Medical Campus, Aurora.
Circulation
|July 21, 2022
概括
一种新的长非编码RNA,Trdn-as,通过调节三结合,对维持心脏功能至关重要. 缺少它会影响的处理,增加心律失常的风险.
科学领域:
- 心脏病学
- 分子生物学
- 遗传学
背景情况:
- 异常的 (Ca2+) 稳定与心律失常和心力衰竭有关.
- 在心肌细胞中对Ca2+处理至关重要,影响Trisk32水平的突变会导致心脏功能障碍.
- 控制心脏中三异形成分的机制尚不清楚.
研究的目的:
- 研究心肌细胞特异性长非编码RNA,Trdn-as在调节心脏功能和三基因拼接中的作用.
- 阐明Trdn-as影响三水平和心肌细胞处理的分子机制.
主要方法:
- 在人类心脏扩张和Trdn-as淘汰小鼠模型中分析三素表达.
- 评估心脏功能和心律失常使用心电图和catecholamine挑战.
- 在心肌细胞中测量Ca2+过渡物.
- 使用生物化学,RNA测序和分子救援试验.
主要成果:
- 在小鼠中,Trdn-as敲除导致心脏三原蛋白减少,Ca2+处理受损,心律不整的易感增加.
- 心脏三素水平的正常化恢复了绝杀心肌细胞的Ca2+处理.
- 与心肌细胞核中的拼接因子相互作用,促进它们与三素前体mRNA的结合.
结论:
- Trdn-as通过三基因的替代拼接来调节心脏功能,这代表了长非编码RNA控制的新机制.
- 针对Trdn-as或替代拼接途径为心脏病提供了潜在的治疗策略.
相关概念视频
Alternative RNA Splicing
21.6K
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...
21.6K
RNA Splicing
56.7K
Splicing is the process by which eukaryotic RNA is edited before its translation into protein. The RNA strand transcribed from eukaryotic DNA is called the primary transcript. The primary transcripts that become mRNAs are called precursor messenger RNAs (pre-mRNAs). Eukaryotic pre-mRNA contains alternating sequences of exons and introns. Exons are nucleotide sequences that code for proteins, whereas introns are the non-coding regions. In RNA splicing, introns are removed and exons are bonded...
56.7K
lncRNA - Long Non-coding RNAs
8.8K
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...
8.8K
Chromatin Structure Regulates pre-mRNA Processing
7.1K
In eukaryotic cells, nascent mRNA transcripts need to undergo many post-transcriptional modifications to reach the cell cytoplasm and translate into functional proteins. For a long time, transcription and pre-mRNA processing were considered two independent events that occur sequentially in the cell. However, it has now been well established that transcription and pre-mRNA processing are two simultaneous processes that are precisely regulated inside the cell.
The chromatin structure, especially...
The chromatin structure, especially...
7.1K
Cardiomyopathy IV: Restrictive Cardiomyopathy
23
Restrictive cardiomyopathy (RCM) is a rare heart muscle disease characterized by impaired ventricular filling due to stiffened ventricular walls, leading to significant diastolic dysfunction.EtiologyRestrictive cardiomyopathy can arise from both inherited and acquired diseases, many of which are systemic. It is categorized into four main types: infiltrative, storage, non-infiltrative, and endomyocardial diseases.Infiltrative diseases, such as amyloidosis, lead to RCM by depositing amyloid...
23
Regulation of Expression at Multiple Steps
990
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...
990


