Signature changes in the expressions of protein-coding genes, lncRNAs, and repeat elements in early and late cellular senescence

Authors: GÖKHAN KARAKÜLAH, CİHANGİR YANDIM

Abstract: Replicative cellular senescence is the main cause of aging. It is important to note that early senescence is linked to tissue regeneration, whereas late senescence is known to trigger a chronically inflammatory phenotype. Despite the presence of various genome-wide studies, there is a lack of information on distinguishing early and late senescent phenotypes at the transcriptome level. Particularly, the changes in the noncoding RNA portion of the aging cell have not been fully elucidated. By utilising RNA sequencing data of fibroblasts, hereby, we are not only reporting changes in gene expression profiles and relevant biological processes in the early and late senescent phenotypes but also presenting significant differences in the expressions of many unravelled long noncoding RNAs (lncRNAs) and transcripts arisen from repetitive DNA. Our results indicate that, in addition to previously reported L1 elements, various LTR and DNA transposons, as well as members of the classical satellites including HSAT5 and α-satellites (ALR/Alpha), are expressed at higher levels in late senescence. Moreover, we revealed finer links between the expression levels of repeats with the genes located near them and known to be involved in cell cycle and senescence. Noncoding elements reported here provide a new perspective to be explored in further experimental studies.

Keywords: Senescence, senescence-associated-secretory phenotype, lncRNA, repetitive DNA, repeatome, repeat elements, bioinformatics, genomics, transcriptome, RNA-seq

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