Role of Non-coding RNAs in Cystic Fibrosis

  • Varilh J
  • Bonini J
  • Taulan-Cadars M
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Abstract

Cystic Fibrosis (CF) is a common autosomal recessive disorder, caused by mutations in the Cystic Fibrosis Transmembrane conductance Regulator (CFTR) gene. CFTR gene expression is tightly controlled by transcriptional and post-transcriptional regulatory factors, resulting in complex spatial and temporal expression patterns. Here, we describe an overview of the findings about the contribution of ncRNAs, especially miRNAs, in physiological CFTR gene expression and in CF. Determination of mechanisms governing its expression is essential for developing new CF therapies. ncRNAs, including lncRNAs and miRNAs, could also contribute to CF progression and severity and their dysregulation in CF opens new perspectives for patient follow-up and treatment.

Figures

  • Figure 1. Non-coding RNAs.
  • Figure 2. lncRNAs, from biogenesis to functions.
  • Figure 3. Genomic locations of miRNAs. miRNA genes, isolated or in clusters, are located in intergenic (ex: miR-494) or intragenic genome regions, including exons of non-coding (e.g. miR-155) or coding (e.g. miR-985) genes and introns of non-coding (e.g. the miR-15a ~16-1 cluster) or coding (e.g. miR-126) genes.
  • Figure 4. Main miRNA roles. a. Translation block by inhibiting cap and poly(A)-binding protein recognition. b. Elon‐ gation inhibition by slowing down elongation or ribosome ‘drop-off’. c. Degradation by deadenylation and decapping. d. Proteolysis. Degradation of a nascent peptide. e. mRNA storage in P-bodies that contain exonucleases, RNA helicas‐ es, decapping enzymes, DCP1/2, exosomes, deadenylases.
  • Table 1. Examples of pulmonary diseases in which miRNAs have a role
  • Figure 5. Approaches for miRNA study. A. Strategies used to study the involvement of miRNAs in the regulation of CFTR gene expression. B. Strategies to identify miRNAs that are deregulated in CF samples compared to non-CF sam‐ ples. Chips for global miRNA profiling are commercialized by Agilent, Affimetrix and Exiqon. miR-seq (miRNA se‐ quencing) is usually performed by Illumina platforms. Luc, luciferase; TLDA, TaqMan Array Micro Fluidic Cards (Applied Biosystems); WT, wild type.
  • Table 2. Free bioinformatics tools for miRNAs
  • Table 3. Free databases for miRNAs

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APA

Varilh, J., Bonini, J., & Taulan-Cadars, M. (2015). Role of Non-coding RNAs in Cystic Fibrosis. In Cystic Fibrosis in the Light of New Research. InTech. https://doi.org/10.5772/60449

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