Abstract
Chimeric RNAs have been recognized as a phenomenon not unique to cancer cells. They also exist in normal physiology. Aging is often characterized by deregulation of molecular and cellular mechanisms, including loss of heterochromatin, increased transcriptional noise, less tight control on alternative splicing, and more stress-induced changes. It is thus assumed that chimeric RNAs are more abundant in older people. In this study, we conducted a preliminary investigation to identify any chimeric RNAs with age-based trends in their expression levels in blood samples. A chimeric RNA candidate list generated by bioinformatic analysis indicated the possibility of both negative and positive trends in the expression of chimeric RNAs. Out of this candidate list, five novel chimeric RNAs were successfully amplified in multiple blood samples and then sequenced. Although primary smaller sample sizes displayed some weak trends with respect to age, analysis of quantitative PCR data from larger sample sizes showed essentially no relationship between expression levels and age. Altogether, these results indicate that, contradictory to the common assumption, chimeric RNAs as a group are not all higher in older individuals and that placing chimeric RNAs in the context of aging will be a much more complex task than initially anticipated.
Highlights
It was thought that chimeric RNA events were exclusively characteristic of the cells of neoplasms [1], but evidence has shown the presence of chimeric RNAs in various physiologically normal tissue [2,3]
Because of their presence in cancers, fusion RNAs were once thought to be the sole result of chromosomal translocations [4], but other work has recently shown that they can exist without DNA arrangement and rather through two mechanisms called cis-splicing of adjacent genes [5,6,7,8], and trans-splicing [9]
The occurrence and frequencies of candidate fusion RNAs were correlated to gender, age, race, ethnicity, height, weight, and Body Mass Index (BMI)
Summary
It was thought that chimeric RNA events were exclusively characteristic of the cells of neoplasms [1], but evidence has shown the presence of chimeric RNAs in various physiologically normal tissue [2,3]. Because of their presence in cancers, fusion RNAs were once thought to be the sole result of chromosomal translocations [4], but other work has recently shown that they can exist without DNA arrangement and rather through two mechanisms called cis-splicing of adjacent genes (cis-SAGe) [5,6,7,8], and trans-splicing [9]. Most indisputable is the genome damage that accompanies aging in organisms, but just how that damage affects cell and tissue function and vitality is more complex
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