ADAR1 Isoforms Regulate Processing in Idiopathic Pulmonary Fibrosis

Overview

Journal Int J Mol Sci

Publisher MDPI

Specialties Biochemistry
Chemistry
Molecular Biology

Date 2022 Aug 26

PMID 36012303

Authors

Gabriela Diaz-Pina

Karla Rubio

Rosa M Ordonez-Razo

Guillermo Barreto

Eduardo Montes

Carina Becerril

Alfonso Salgado

Hector Cabrera-Fuentes

Arnoldo Aquino-Galvez

Angeles Carlos-Reyes

Victor Ruiz

Affiliations

Soon will be listed here.

Abstract

Double-stranded RNA adenosine deaminase 1 (ADAR1) is significantly down-regulated in fibroblasts derived from Idiopathic Pulmonary Fibrosis (IPF) patients, and its overexpression restored levels of , , and . There are two ADAR1 isoforms in humans, ADAR1-p110 and ADAR1-p150, generated by an alternative promoter. is considered an essential microRNA in Pulmonary Fibrosis (PF). In silico analysis revealed and , proteins involved in the development of IPF, as targets. We analyzed the role of ADAR1-p110 and ADAR1-p150 isoforms in the regulation of maturation and the effect of this regulation on the expression of and in IPF fibroblast. We demonstrated that differential expression and subcellular distribution of ADAR1 isoforms in fibroblasts contribute to the up-regulation of and down-regulation of mature . Induction of overexpression of ADAR1 reestablishes the expression of and in lung fibroblasts. The reduction of mature upregulates the expression of and . Thus, ADAR1 isoforms and could have a synergistic role in IPF, which is a promising explanation in the mechanisms of fibrosis development, and the regulation of both molecules could be used as a therapeutic approach in IPF.

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References

Crews L, Jiang Q, Zipeto M, Lazzari E, Court A, Ali S . An RNA editing fingerprint of cancer stem cell reprogramming. J Transl Med. 2015; 13:52. PMC: 4341880. DOI: 10.1186/s12967-014-0370-3. View

Luciano D, Mirsky H, Vendetti N, Maas S . RNA editing of a miRNA precursor. RNA. 2004; 10(8):1174-7. PMC: 1370607. DOI: 10.1261/rna.7350304. View

Selman M, Pardo A, Kaminski N . Idiopathic pulmonary fibrosis: aberrant recapitulation of developmental programs?. PLoS Med. 2008; 5(3):e62. PMC: 2265304. DOI: 10.1371/journal.pmed.0050062. View

Pandit K, Milosevic J, Kaminski N . MicroRNAs in idiopathic pulmonary fibrosis. Transl Res. 2011; 157(4):191-9. DOI: 10.1016/j.trsl.2011.01.012. View

Rubio K, Castillo-Negrete R, Barreto G . Non-coding RNAs and nuclear architecture during epithelial-mesenchymal transition in lung cancer and idiopathic pulmonary fibrosis. Cell Signal. 2020; 70:109593. DOI: 10.1016/j.cellsig.2020.109593. View

Desterro J, Keegan L, Lafarga M, Berciano M, OConnell M, Carmo-Fonseca M . Dynamic association of RNA-editing enzymes with the nucleolus. J Cell Sci. 2003; 116(Pt 9):1805-18. DOI: 10.1242/jcs.00371. View

Yang B, Hu P, Lin X, Han W, Zhu L, Tan X . PTBP1 induces ADAR1 p110 isoform expression through IRES-like dependent translation control and influences cell proliferation in gliomas. Cell Mol Life Sci. 2015; 72(22):4383-97. PMC: 11114032. DOI: 10.1007/s00018-015-1938-7. View

Kis K, Liu X, Hagood J . Myofibroblast differentiation and survival in fibrotic disease. Expert Rev Mol Med. 2011; 13:e27. PMC: 5675569. DOI: 10.1017/S1462399411001967. View

Nishikura K . Functions and regulation of RNA editing by ADAR deaminases. Annu Rev Biochem. 2010; 79:321-49. PMC: 2953425. DOI: 10.1146/annurev-biochem-060208-105251. View

10.

Brummer A, Yang Y, Chan T, Xiao X . Structure-mediated modulation of mRNA abundance by A-to-I editing. Nat Commun. 2017; 8(1):1255. PMC: 5665907. DOI: 10.1038/s41467-017-01459-7. View

11.

Orlandi C, Barbon A, Barlati S . Activity regulation of adenosine deaminases acting on RNA (ADARs). Mol Neurobiol. 2011; 45(1):61-75. DOI: 10.1007/s12035-011-8220-2. View

12.

Sansam C, Wells K, Emeson R . Modulation of RNA editing by functional nucleolar sequestration of ADAR2. Proc Natl Acad Sci U S A. 2003; 100(24):14018-23. PMC: 283538. DOI: 10.1073/pnas.2336131100. View

13.

Huleihel L, Ben-Yehudah A, Milosevic J, Yu G, Pandit K, Sakamoto K . Let-7d microRNA affects mesenchymal phenotypic properties of lung fibroblasts. Am J Physiol Lung Cell Mol Physiol. 2014; 306(6):L534-42. PMC: 3949080. DOI: 10.1152/ajplung.00149.2013. View

14.

Yang W, Chendrimada T, Wang Q, Higuchi M, Seeburg P, Shiekhattar R . Modulation of microRNA processing and expression through RNA editing by ADAR deaminases. Nat Struct Mol Biol. 2005; 13(1):13-21. PMC: 2950615. DOI: 10.1038/nsmb1041. View

15.

Faller M, Guo F . MicroRNA biogenesis: there's more than one way to skin a cat. Biochim Biophys Acta. 2008; 1779(11):663-7. PMC: 2633599. DOI: 10.1016/j.bbagrm.2008.08.005. View

16.

Heale B, Keegan L, McGurk L, Michlewski G, Brindle J, Stanton C . Editing independent effects of ADARs on the miRNA/siRNA pathways. EMBO J. 2009; 28(20):3145-56. PMC: 2735678. DOI: 10.1038/emboj.2009.244. View

17.

Zipeto M, Court A, Sadarangani A, Delos Santos N, Balaian L, Chun H . ADAR1 Activation Drives Leukemia Stem Cell Self-Renewal by Impairing Let-7 Biogenesis. Cell Stem Cell. 2016; 19(2):177-191. PMC: 4975616. DOI: 10.1016/j.stem.2016.05.004. View

18.

Rubio K, Singh I, Dobersch S, Sarvari P, Gunther S, Cordero J . Inactivation of nuclear histone deacetylases by EP300 disrupts the MiCEE complex in idiopathic pulmonary fibrosis. Nat Commun. 2019; 10(1):2229. PMC: 6527704. DOI: 10.1038/s41467-019-10066-7. View

19.

Kim V . MicroRNA biogenesis: coordinated cropping and dicing. Nat Rev Mol Cell Biol. 2005; 6(5):376-85. DOI: 10.1038/nrm1644. View

20.

Martinez F, Collard H, Pardo A, Raghu G, Richeldi L, Selman M . Idiopathic pulmonary fibrosis. Nat Rev Dis Primers. 2017; 3:17074. DOI: 10.1038/nrdp.2017.74. View