Are Long Intergenic Non-ccoding RNAs Central Regulators of Inflammation and the Innate Immune Response?

Project: Research council

Project Details

Description

Upon completion of the human genome project, the biggest surprise was that humans have far fewer genes than previously expected (~ 21,000). Additionally, less than 2% of the available DNA directly codes for these genes. To address this paradox, recent studies have suggested that much of the remaining 98% of DNA is turned into 'non-coding RNA' and that these are important regulators of gene expression. For convenience, we commonly divide this non-coding RNA into small non-coding RNAs and long non-coding RNAs. At the present time, we have little idea about the role of the majority of this non-coding RNA although recent studies have indicated that specific non-coding RNAs may regulate the immune response. In order to fight infection by bacteria, fungi and viruses, the body has a complex defense system called the immune response. This involves the recognition of these micro-organisms and release of a range of chemicals that recruit and activate immune cells (inflammation) that are involved in removing these un-wanted invaders. Under normal conditions, this inflammatory response is then switched off. However, under certain circumstances, prolonged activation can be life-threatening or lead to the development of common conditions such as asthma, diabetes, cancer and cardiovascular disease. For this reason it is important to understand the mechanisms that regulate both the activation and inhibition of this immune response. Previous studies have shown that this immune response is altered by a family of small non-coding RNAs, called microRNAs. However, whether long non-coding RNAs might also be important is unknown. In preliminary studies, we have shown that the levels of a number of long non-coding is increased in cells following stimulation with a product made from bacteria. We also found that one of these long non-coding RNAs regulates the release of the chemicals that are used to kill the invading micro-organisms. In this project, we will extend these studies to examine what other long non-coding RNAs do and how they might exert their actions. Overall, we believe that these investigations will show that long non-coding RNAs are important regulators of inflammation and the immune response to invading pathogens.
StatusFinished
Effective start/end date3/04/132/04/16

Funding

  • Biotechnology and Biological Sciences Research Council

RCUK Research Areas

  • Immunology

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  • Research Output

    • 6 Article
    • 1 Literature review

    Divergent signalling pathways regulate lipopolysaccharide-induced eRNA expression in human monocytic THP1 cells

    Heward, J. A., Roux, B. T. & Lindsay, M. A., 30 Jan 2015, In : FEBS Letters. 589, 3, p. 396-406 11 p.

    Research output: Contribution to journalArticle

    Open Access
    File
  • 4 Citations (Scopus)
    101 Downloads (Pure)

    LincRNA signatures in human lymphocytes

    Roux, B. T. & Lindsay, M. A., Mar 2015, In : Nature Immunology. 16, 3, p. 220-222 3 p.

    Research output: Contribution to journalArticle

    Open Access
    File
  • 4 Citations (Scopus)
    239 Downloads (Pure)

    Emerging role of microRNAs and long noncoding RNAs in respiratory disease

    Booton, R. & Lindsay, M. A., Jul 2014, In : Chest. 146, 1, p. 193-204 12 p.

    Research output: Contribution to journalLiterature review

    Open Access
    File
  • 79 Citations (Scopus)
    210 Downloads (Pure)