Epigenetics is the study of heritable changes in phenotype that are the result of things other than changes in the DNA sequence itself. The field includes histone modifications, DNA methylation patterns and non-coding RNA expression. All of which are involved in the regulation of gene expression. Whilst the central dogma of genetics may suggest that all RNA is translated into protein, non-coding RNAs have been known of for many years. The most obvious examples would be ribosomal RNA (rRNA) or transfer RNA (tRNA). However, recent projects such as ENCODE (1) report that whilst only ~3 % of the genome is translated into protein, in the region of 62-85 % of the genome is transcribed into RNA. This means that the vast majority of RNA is non-coding. This non-coding RNA has been divided into multiple classes including: rRNA; tRNA; PIWI-interacting RNA (piRNA); small nucleolar RNA (snoRNA); long non-coding RNA (lncRNA); microRNA (miRNA); transcribed ultra-conserved regions (T-UCR); and, anti-sense transcripts. There are also many failed / stalled transcripts leading to debate about the exact amount of overall transcription that is functional. However, it is clear that the vast majority of RNA produced in the cell is non-coding and that much of this is functional. The recent focus on non-coding RNA has largely been on miRNA. MiRNAs are short (~22 nucleotide) RNA molecules that primarily bind to the 3′ UTR of messenger RNA (mRNA) molecules either preventing translation of mRNA or targeting the mRNA for degradation. They were first discovered in C. elegans in 1993 but are now known to be widespread throughout animals, plants and viruses. In humans there are only 1881 known miRNAs (http://www.miRBase.org accessed 2015 Mar 27). However, each miRNA binds to multiple mRNAs and each mRNA is bound by multiple miRNAs. Thus, miRNAs comprise a highly complex network for the fine tuning of gene expression. MiRNAs have been shown to be altered by diet and exercise and are likely to be involved in the normal physiological response to a number of stimuli (2). They have also been shown to be consistently altered in many disease states suggesting that they are part of the physiological response to disease, or involved in the development of disease itself (3). More recently, miRNAs have also been observed in plasma (4). Initially, these were thought to be debris from damaged or dying cells; however, they are also released by healthy cells and are consistently altered in specific disease states. Furthermore, they appear to be actively secreted, with miRNAs released by cells in differing proportions to the miRNAs within those cells. These circulating miRNAs (c-miRNAs) have been shown to be taken up by recipient cells and alter gene expression within the recipient cells, suggesting that they are involved in cell-cell communication. Thus, they are not only useful biomarkers of disease but may also have some function in the circulation. One of the most intriguing miRNA findings in recent years was the identification of plant miRNAs in the plasma of individuals who consume large quantities of rice. However, we and others have failed to replicate this and debate remains about the functionality of such trans-kingdom miRNAs. Like tissue miRNAs, c-miRNAs have also been shown to be altered by exercise (5) and disease (4). We have shown that c-miRNAs differ between endurance athletes and strength athletes (6). We have also shown c-miRNAs to respond to 6 weeks of olive oil supplementation in humans (unpublished). In the space of a few years we have moved from having little understanding of miRNAs with most research focusing on their involvement in cancer, to having vast amounts of data on miRNA involvement in numerous situations. As we recognise more sub-classes of non-coding RNA and begin to investigate their response to common stimuli, it seems likely that more non-coding RNA molecules will be implicated in the physiological response to diet, exercise and disease. T-UCRs are a class of long non-coding RNA that have been shown to be dysregulated in cancer (7). There are 481 known human T-UCRs. However, little data exists on their normal cellular function, or on their response to common stimuli. We investigated the expression of T-UCRs from skeletal muscle biopsies of human volunteers (n=20) at 0 hrs and 2 hrs of an oral glucose tolerance test, before and after a period of high-fat feeding. We showed that 53 % of T-UCRs are expressed at appreciable levels in skeletal muscle and using a pooled sample approach, identified T-UCRs which either responded to glucose feeding during the OGTT, or to hyper-caloric high fat feeding. Understanding the response of the myriad of non-coding RNA molecules to common stimuli will be crucial to developing a full understanding of human physiology.