An intriguing RNA species--perspectives of circularized RNA.

Ting Shen,Gang Wei,Miao Han,Ting Ni

doi:10.1007/s13238-015-0202-0

Abstract

Circular RNAs (circRNAs), a kind of covalently closed RNA molecule, were used to be considered a type of by-products of mis-splicing events and were discovered sporadically due to the technological limits in the early years. With the great technological progress such as high-throughput next-generation sequencing, numerous circRNAs have recently been detected in many species. CircRNAs were expressed in a spatio-temporally specific manner, suggesting their regulatory functional potentials were overlooked previously. Intriguingly, some circRNAs were indeed found with critical physiological functions in certain circumstances. CircRNAs have a more stable molecular structure that can resist to exoribonuclease comparing to those linear ones, and their molecular functions include microRNA sponge, regulatory roles in transcription, mRNA traps that compete with linear splicing, templates for translation and possibly other presently unknown roles. Here, we review the discovery and characterization of circRNAs, the origination and formation mechanism, the physiological functions and the molecular roles, along with the methods for detection of circRNAs. We further look into the future and propose key questions to be answered for these magical RNA molecules.

Highlights

CircRNA is a member of the non-coding RNA kingdom
Some circRNAs were found with critical physiological functions in certain circumstances
CircRNAs have a more stable molecular structure that can resist to exoribonuclease comparing to those linear ones, and their molecular functions include microRNA sponge, regulatory roles in transcription, mRNA traps that compete with linear splicing, templates for translation and possibly other presently unknown roles

Summary

INTRODUCTION

CircRNA is a member of the non-coding RNA kingdom. Unlike the traditionally known RNA species, sequence of circRNA is not arranged in a normal order relative to the genomic context but arrays in a scrambled manner, in which the 3′ downstream sequences are joined to the 5′ upstream sequences, resulting in a covalent-closed circular molecule without free terminals, resemble that of plasmids. The main feature of circRNA is the intramolecular circular structure wherein the 3′ ends of some exons turns back and joins the 5′ ends of other upstream exons to form a closed molecule Unlike those typical linear RNAs, the 5′ cap and 3′ polyadenylation tail (poly-(A) tail) are absent in these transcripts. Recent investigations have suggested four possible biological functions of circRNAs (Fig. 1); they can serve as microRNA sponges (Hansen et al, 2013; Memczak et al, 2013), promoting transcription of parent gene (Li et al, 2015; Zhang et al, 2013), mRNA traps (competing with linear splicing) (Ashwal-Fluss et al, 2014; Chao et al, 1998), and templates for translation (Surono et al, 1999; Wang and Wang, 2014).

Translation Peptide

METHODS

CONCLUSION AND PERSPECTIVE

Findings

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