Gallop Racing Shifts Mature mRNA towards Introns: Does Exercise-Induced Stress Enhance Genome Plasticity?

Abstract

Physical exercise is universally recognized as stressful. Among the "sport species", the horse is probably the most appropriate model for investigating the genomic response to stress due to the homogeneity of its genetic background. The aim of this work is to dissect the whole transcription modulation in Peripheral Blood Mononuclear Cells (PBMCs) after exercise with a time course framework focusing on unexplored regions related to introns and intergenic portions. PBMCs NGS from five 3 year old Sardinian Anglo-Arab racehorses collected at rest and after a 2000 m race was performed. Apart from differential gene expression ascertainment between the two time points the complexity of transcription for alternative transcripts was identified. Interestingly, we noted a transcription shift from the coding to the non-coding regions. We further investigated the possible causes of this phenomenon focusing on genomic repeats, using a differential expression approach and finding a strong general up-regulation of repetitive elements such as LINE. Since their modulation is also associated with the "exonization", the recruitment of repeats that act with regulatory functions, suggesting that there might be an active regulation of this transcriptional shift. Thanks to an innovative bioinformatic approach, our study could represent a model for the transcriptomic investigation of stress.Genes 2020, 11, 410 2 of 15 in humans [1] and in animals with other ongoing initiatives such Functional Annotation of Animal Genomes (FAANG) [2].Despite new knowledge has been produced and genome annotations significantly improved, the genome response, in terms of gene expression modulation, is far from being understood. The big annotation projects, with some exceptions (FANTOM Projects [3]), focused mostly on "spatial" variation, intended as variation of expression in different cells and tissues, while the "temporal" one, physiological and pathological variation through time, has been left behind. This is particularly true for "non-model" species.Also different studies (Genome Wide Association Studies-GWAS) pointed towards the intergenic and intronic fraction of the genome [4] where the most regulatory molecules lie and are transcribed.One of the most promising approach in the dissection of the molecular basis of a phenotype is the Expression Quantitative Trait Loci (eQTL), where variations on gene expression are associated to specific regions or variants in the DNA. Studies in eQTL are already possible and are being applied, but the real step forward in functional genomics could be made by analyzing temporal data other than only the spatial ones, understanding "when" and "how much" the existing DNA variation could affect the transcriptional machinery, and therefore the phenotype. This is especially true when we are facing with biological problems involving a complex multi-organ process such exercise and stress related organism response.Time-course experiments may allow to fully understand the functional response of the genome to stimuli when pathway...

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