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lncRNA - Long Non-coding RNAs02:39

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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...
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Rapidly dividing tumors, embryos, and wounded tissues require more oxygen than usual, lowering the oxygen concentration in the blood. At low oxygen or hypoxic conditions, an oxygen-sensitive transcription factor called the hypoxia-inducible factor 1 or HIF1 is activated. HIF1 is a dimeric protein of alpha (ɑ) and beta (β) subunits.  Under optimal oxygen conditions, HIF1β is present in the nucleus while HIF1ɑ remains in the cytosol. HIF1ɑ is hydroxylated by prolyl...
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Blood vessel formation starts early during embryonic development, around day 7. In the extraembryonic yolk sac, mesodermal precursor cells called hemangioblast proliferate and differentiate into angioblast. Angioblasts express vascular endothelial growth factor receptor 2 or VEGFR2, which binds VEGF-A, a proangiogenic factor, guiding blood vessel formation. VEGF signaling promotes angioblasts to form a blood island in the developing embryo. Angioblasts further differentiate, giving rise to...
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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...
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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...
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长非编码RNA曼蒂斯促进内皮血管功能

Matthias S Leisegang1, Christian Fork1, Ivana Josipovic1

  • 1From Institute for Cardiovascular Physiology (M.S.L., C.F., I.J., M.J.M., J.E., F.M., R.P.B.), Functional Proteomics, SFB 815 Core Unit, Faculty of Medicine (F.M.R., J.H., I.W.), Institute of Vascular Signalling (J.H.), Institute of Cardiovascular Regeneration (P.H. Y.P., S.U., K.S., R.A.B., S.D.), Department of Neurosurgery (T.M.F.), Pharmazentrum Frankfurt, Institute of General Pharmacology and Toxicology (K.D.), Goethe University, Germany; ECCPS Bioinformatics and Sequencing Facility (J.P., S.G., C.K., M.L.) and Department of Lung Development and Remodeling (C.V., S.S.P.), Max-Planck-Institute for Heart and Lung Research, Bad Nauheim, Germany; Institute of Neurology (K.H.P., M.M., K.D.); Department of Vascular and Endovascular Surgery, Klinikum Rechts der Isar, Technical University Munich, Germany (L.M.); Luxembourg Centre of Neuropathology (M.M.); Laboratoire National de Santé, Dudelange, Luxembourg (M.M.); Luxembourg Centre for Systems Biomedicine, University of Luxembourg, Esch-sur-Alzette (M.M.); NORLUX Neuro-Oncology Laboratory, Department of Oncology, Luxembourg Institute of Health (M.M.); Cardiovascular Innovation Institute, University of Louisville, KY (S.U.); Department of Internal Medicine, Member of the German Center for Lung Research (DZL), Justus-Liebig University, Giessen, Germany (R.T.S., N.W., S.S.P.); Department of Medicine, Duke University and Durham VA Medical Center, NC (F.J.M.); and German Center of Cardiovascular Research (DZHK), Partner Site RheinMain, Frankfurt, Germany (M.S.L., C.F., I.J., J.H., J.E., P.H., F.M., Y.P., K.H.P., K.S., I.W., R.A.B., S.D., R.P.B.).

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PubMed
概括
此摘要是机器生成的。

这项研究确定MANTIS是一种新型长非编码RNA (lncRNA),对内皮细胞功能和血管生成至关重要. 曼蒂斯通过与染色体重塑复合体相互作用来调节基因转录.

关键词:
长非编码的RNA表观遗传学质母细胞瘤高血压,肺部疾病新血管化,生理

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科学领域:

  • 分子生物学
  • 遗传学
  • 细胞生物学

背景情况:

  • 内皮细胞的血管功能至关重要,但不完全理解.
  • 长非编码RNAs (lncRNAs) 在内皮细胞调节中的作用在很大程度上尚未被探索.

研究的目的:

  • 识别功能性显著的新型内皮内核RNA.
  • 研究已识别的 lncRNA 的调节机制和功能影响.

主要方法:

  • 在人类静脉内皮细胞中进行外阵列分析和JARID1B敲除.
  • 基因组分离,质谱测量,ChIP-seq,CRISPR-Cas9,以及基因表达分析.
  • 对患者样本 (肺,质母细胞瘤) 和动物模型 (动脉样硬化,肺高血压) 的分析.

主要成果:

  • 确定MANTIS (lncRNA n342419) 是一个关键的表观基因调节 lncRNA.
  • 在肺高血压,动脉样硬化和质母细胞瘤中,MANTIS的表达变化.
  • 曼蒂斯的删除/沉默会损害内皮细胞血管生成和剪切应激反应.
  • 曼蒂斯与BRG1相互作用,调节关键内皮基因 (SOX18,SMAD6,COUP-TFII) 的染色体重塑和转录.

结论:

  • 曼蒂斯是一种新型,差异调节的 lncRNA.
  • 曼蒂斯在促进内皮血管功能方面发挥着至关重要的作用.
  • 曼蒂斯是血管疾病的潜在治疗点.