Regulation of mRNA turnover in cystic fibrosis lung disease

Abstract

Cystic fibrosis (CF) is an autosomal recessive disease due to mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene, F508del-CFTR being the most frequent mutation. The CF lung is characterized by a hyperinflammatory phenotype and is regulated by multiple factors that coordinate its pathophysiology. In CF the expression of CFTR as well as proinflammatory genes are regulated at the level of messenger RNA (mRNA) stability, which subsequently affect translation. These mechanisms are mediated by inflammatory RNA-binding proteins as well as small endogenous noncoding microRNAs, in coordination with cellular signaling pathways. These regulatory factors exhibit altered expression and function in vivo in the CF lung, and play a key role in the pathophysiology of CF lung disease. In this review, we have described the role of mRNA stability and associated regulatory mechanisms in CF lung disease. WIREs RNA 2017, 8:e1408. doi: 10.1002/wrna.1408 For further resources related to this article, please visit the WIREs website.

Integrated Analysis of lncRNA and mRNA Transcriptomes Reveals New Regulators of Ubiquitination and the Immune Response in Silica-Induced Pulmonary Fibrosis

“…Laurent et al explored the cultured lung fibroblast transcriptome of idiopathic pulmonary fibrosis; mRNAs encoding LIMS2, ASB1, and HHAT were upregulated and those encoding TRANK1, IFIT1, and SLC15A3 were downregulated [37]. Biswas et al found that, in cystic fibrosis, CTFR expression was regulated at the mRNA level [38]. Certain mRNAs associated with lung inflammation (including that encoding IL-8) were appeared to be a regulator of other miRNAs biogenesis in lung epithelial cells, showing they were potential candidates for anti-inflammatory therapeutics for cystic fibrosis [39, 40].…”