Asthma and the regulated retrotransposon transcriptome: Figure 1–

Abstract

To the Editors: Asthma is a complex disease characterised by inflammation and remodelling of the airways. Over the past few decades enormous progress has been made to understand which genes are associated with asthma development and several interactions between genes and environmental factors have been elucidated. Investigations into genetic and gene expression profiling, as well as single nucleotide polymorphism analyses, have helped to better understand the underlying molecular mechanisms of asthma. However, the recent identification of novel regulatory functions for transposable and transposed genetic elements (TEs) may be an important and new key to help understand the genetics that cause the heterogeneous manifestations of the asthma pathology. Approximately 45% of the human genome is made of TEs [1]. The vast majority of TEs originate from retrotransposition of genetic elements known as short and long interspersed nuclear elements, long terminal repeat-superfamilies and direct transposition of TE-containing genomic DNA. Formerly regarded as junk DNA, it is now becoming increasingly evident that TEs often function to regulate and fine tune gene expression [2, 3]. TE-driven transcription frequently controls the expression of protein coding genes via alternative promoters, cis-regulatory non-protein-coding RNAs and through the formation of double stranded short RNAs. Faulkner and Carninci [3] demonstrated that transcription initiation from promoters present in TEs is a general phenomenon, even when they are corrupted and not easily recognised as genuine transposons. In addition, TE insertions into gene sequences affect RNA stability and splicing variants [4, 5]. Approximately 30% of human mRNA contains at least one retrotransposon, and the mRNA levels were shown to be inversely proportional to the percentage of retrotransposons [6]. Such findings suggest that TEs are intrinsic components of the transcriptional …