Related Experiment Video
Updated: Aug 30, 2025
08:09
Vasodilation of Isolated Vessels and the Isolation of the Extracellular Matrix of Tight-skin Mice
Published on: March 24, 2017
8.2K
ADAR1 Isoforms Regulate Let-7d Processing in Idiopathic Pulmonary Fibrosis
Gabriela Díaz-Piña1, Karla Rubio2,3,4, Rosa M Ordoñez-Razo5
1Molecular Biology Laboratory, Pulmonary Fibrosis Department, National Institute of Respiratory Diseases "Ismael Cosío Villegas", Calzada de Tlalpan No. 4502, Col. Sección XVI, Mexico City 14080, Mexico.
International Journal of Molecular Sciences
|August 26, 2022
Summary
Double-stranded RNA adenosine deaminase 1 (ADAR1) isoforms are dysregulated in Idiopathic Pulmonary Fibrosis (IPF), affecting Let-7d microRNA maturation. This impacts COL3A1 and SMAD2 expression, suggesting a therapeutic target for fibrosis.
Area of Science:
- Biochemistry
- Molecular Biology
- Pulmonary Medicine
Background:
- Idiopathic Pulmonary Fibrosis (IPF) is characterized by fibroblast dysfunction.
- Double-stranded RNA adenosine deaminase 1 (ADAR1) is downregulated in IPF fibroblasts.
- ADAR1 has two isoforms, p110 and p150, with distinct functions.
Purpose of the Study:
- To investigate the role of ADAR1 isoforms in regulating Let-7d microRNA maturation in IPF.
- To determine the impact of ADAR1-mediated Let-7d regulation on COL3A1 and SMAD2 expression in IPF fibroblasts.
- To explore ADAR1 and Let-7d as potential therapeutic targets for IPF.
Main Methods:
- Analysis of ADAR1 isoform expression and subcellular localization in IPF fibroblasts.
- Assessment of pri-miR-Let-7d and mature Let-7d levels.
- Measurement of COL3A1 and SMAD2 mRNA expression.
- In silico analysis to identify Let-7d targets.
Main Results:
- Differential expression and distribution of ADAR1 isoforms in IPF fibroblasts lead to increased pri-miR-Let-7d and decreased mature Let-7d.
- ADAR1 overexpression restored pri-miR-Let-7d and Let-7d levels in lung fibroblasts.
- Reduced mature Let-7d levels correlated with increased COL3A1 and SMAD2 expression.
Conclusions:
- ADAR1 isoforms and Let-7d play a synergistic role in IPF pathogenesis.
- Dysregulation of ADAR1 and Let-7d contributes to fibrosis development.
- Targeting ADAR1 and Let-7d offers a potential therapeutic strategy for IPF.
Related Concept Videos
01:22MicroRNAs
3.1K
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...
3.1K
01:31Regulation of the Unfolded Protein Response
2.6K
Inositol-requiring kinase one or IRE1 is the most conserved eukaryotic unfolded protein response (UPR) receptor. It is a type I transmembrane protein kinase receptor with a distinctive site-specific RNase activity. As the binding mechanics of the misfolded proteins with the N-terminal domain of IRE-1 are unclear, three binding models — direct, indirect, and allosteric -- are proposed for receptor activation. Nevertheless, it is known that once a misfolded protein associates with IRE1, it...
2.6K
01:30Pulmonary Hypertension: Classification and Pathogenesis
272
Pulmonary hypertension (PH) is a severe health condition in which the mean pulmonary arterial pressure increases to 25 mmHg or more, even when the body is at rest. This high pressure in the blood vessels that transport blood from the heart to the lungs can cause various symptoms, including shortness of breath, can lead to right heart failure, and significantly affect the overall quality of life.
There are various classifications for PH, each relating to different underlying causes and also...
There are various classifications for PH, each relating to different underlying causes and also...
272
02:28Leaky Scanning
5.2K
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...
5.2K
01:23Cystic Fibrosis: Pathogenesis
348
Cystic fibrosis (CF), an autosomal recessive disorder, significantly affects the function of exocrine glands. This genetically inherited disease is characterized by the production of thick and sticky mucus, which can severely affect various organs and systems in the body.
CF is primarily caused by a genetic mutation in a chromosome 7 gene coding for the cystic fibrosis transmembrane conductance regulator (CFTR) protein. The most common gene mutation leading to CF is the ΔF508 mutation,...
CF is primarily caused by a genetic mutation in a chromosome 7 gene coding for the cystic fibrosis transmembrane conductance regulator (CFTR) protein. The most common gene mutation leading to CF is the ΔF508 mutation,...
348
01:32RNA 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