Abstract
Circular RNAs (circRNAs) are an emerging group of long non-coding RNAs (lncRNAs) and have attracted attention again according to the progress in high-throughput sequencing in recent years. circRNAs are genome transcripts produced from pre-messenger (m)RNA regions in a specific process called “back-splicing,” which forms covalently closed continuous loops. Due to their lack of a 5’ cap and 3’ poly-adenylated tails, circRNAs are remarkably more stable than linear RNAs. Functionally, circRNAs can endogenously sponge to microRNAs, interact with RNA-binding proteins (RBPs), or translate themselves. Moreover, circRNAs can be expressed in cell type- or tissue-specific expression patterns. Therefore, they are proposed to play essential roles in fine-tuning our body’s homeostasis by regulating transcription and translation processes. Indeed, there has been accumulating emergent evidence showing that dysregulation of circRNAs can lead to metabolic disorders. This study explored the current knowledge of circRNAs that regulate molecular processes associated with glucose and lipid homeostasis and related pathogeneses of metabolic disorders. We also suggest the potential role of circRNAs as disease biomarkers and therapeutic targets.
Highlights
Statistics from the World Health Organization from 2000 to 2019 reveal that “noncommunicable diseases” accounted for seven of the top 10 causes of death worldwide.Heart disease still ranks first among all diseases [1]
The majority of circRNAs mainly reside in the cytoplasm, while ciRNAs and EIciRNAs are mainly found in nuclei [12,13,15]
CDR1as, which originates from the antisense transcript of the cerebellar degenerationrelated protein 1 gene, was the first circRNA studied in pancreatic β-cells [48,49]
Summary
Statistics from the World Health Organization from 2000 to 2019 reveal that “noncommunicable diseases” accounted for seven of the top 10 causes of death worldwide. While infrastructural types, including ribosomal (r)RNAs, transfer (t)RNAs, and small nuclear (sn)RNAs, are typically constitutively expressed, regulatory types, such as micro (mi)RNAs, long noncoding (lnc)RNAs, circular (circ)RNAs, and piwi-interacting (pi)RNAs, were proposed to fine-tune target gene expressions [5] These special ncRNAs are not necessarily transcribed into proteins but orchestrate gene regulatory networks in a hidden layer [5,6,7]. Due to a lack of suitable research tools, circRNAs were once considered to be “junk” products produced by aberrant RNA splicing They have low abundances in cells and low sequence conservation, and received little attention until 1993, when it was discovered that Sry, the sex-determining gene, undergoes circular transcription in adult mouse testicles [10]. With these new discoveries, people began to recognize that circRNAs are abundant, diverse, and conserved molecules in tissue- and developmental stage-specific manners and might play critical roles in human biological processes [11,12,13]
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