The Biogenesis, Functions, and Challenges of Circular RNAs

Abstract

Covalently closed circular RNAs (circRNAs) are produced by precursor mRNA back-splicing of exons of thousands of genes in eukaryotes. circRNAs are generally expressed at low levels and often exhibit cell-type-specific and tissue-specific patterns. Recent studies have shown that their biogenesis requires spliceosomal machinery and can be modulated by both cis complementary sequences and protein factors. The functions of most circRNAs remain largely unexplored, but known functions include sequestration of microRNAs or proteins, modulation of transcription and interference with splicing, and even translation to produce polypeptides. However, challenges exist at multiple levels to understanding of the regulation of circRNAs because of their circular conformation and sequence overlap with linear mRNA counterparts. In this review, we survey the recent progress on circRNA biogenesis and function and discuss technical obstacles in circRNA studies.

Current status and potential role of circular RNAs in neurological disorders

“…Given the slow division rates of neurons, circRNAs may accumulate to a greater extent in the brain than in other tissues (Zhang et al ). This may explain the observation that some circRNAs are the primary RNA isoforms derived from some neuronal genes (Li et al ).…”

circEPSTI1 regulates ovarian cancer progression via decoying miR‐942

“…10 In non-small cell lung cancer, hsa_circ_0033155 acts as a tumour suppressor to regulate cell proliferation, colony formation and migration. 12 In malignant melanoma, hsa_circ_0025039 promotes cell growth, invasion and glucose metabolism via sponging miR-198. 12 In malignant melanoma, hsa_circ_0025039 promotes cell growth, invasion and glucose metabolism via sponging miR-198.…”

Engineering of hairpin ribozyme variants for RNA recombination and splicing

“…) or intermolecularly (leading to oligomers, not shown). Whereas the first mimics the process of back‐splicing, the latter can be seen as a variant of alternative splicing, in the course of which catalytic exons are ligated to become a carrier of extended genetic information. The reaction has been followed by gel electrophoretic analysis in one or two dimensions, and by atomic force microscopy (AFM) .…”