Abstract
Circular RNAs (circRNAs) have been identified in numerous species, including human, mouse, nematode, and coelacanth. They are believed to function as regulators of gene expression at least in part by sponging microRNAs. Here, we describe the identification of circRNAs in monkey (Rhesus macaque) skeletal muscle. RNA sequencing analysis was employed to identify and annotate ~12,000 circRNAs, including numerous circular intronic RNAs (ciRNAs), from skeletal muscle of monkeys of a range of ages. Reverse transcription followed by real-time quantitative (q)PCR analysis verified the presence of these circRNAs, including the existence of several highly abundant circRNAs, and the differential abundance of a subset of circRNAs as a function of age. Taken together, our study has documented systematically circRNAs expressed in skeletal muscle and has identified circRNAs differentially abundant with advancing muscle age. We propose that some of these circRNAs might influence muscle function.
Highlights
Aging involves the progressive accumulation of deleterious changes in cells, tissues, and organs leading to age-related physiologic declines and diseases [1]
Our study provides a large number of previously unannotated circRNAs in Rhesus monkey and identifies changes in skeletal muscle circRNAs with advancing age, which may impact upon muscle aging and age-related muscle disorders
From the large collection of muscle circRNAs, we found a subset of abundant circRNAs that displayed age-dependent changes, including a group of circRNAs showing reduced abundance with aging (Fig. 2), while virtually no circRNAs showed increased abundance with increasing age
Summary
Aging involves the progressive accumulation of deleterious changes in cells, tissues, and organs leading to age-related physiologic declines and diseases [1]. Contributing to the functional losses and pathologies of aging are changes in gene expression programs, controlled transcriptionally and post-transcriptionally through numerous factors, including regulatory RNAs such as long noncoding (lnc)RNAs and microRNAs [25]. CircRNAs are highly abundant in some tissues and are rather stable molecules [7, 8], at least in part because these RNAs form circles and lack 5’ and 3’ ends. They are generated during splicing and can arise from exons (exonic circRNAs), introns (intronic circRNAs or ciRNAs), or a combination of exons and introns (exon-intron circRNAs or EIciRNAs) [7, 9,10,11]. According to other proposed molecular functions, circRNAs may serve as sponges for RNA-binding proteins (RBPs), provide platforms for assembly of RBPs, and associate with mRNAs and modulate their expression post-transcriptionally [12]
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