Thrown for a (stem) loop: How RNA structure impacts circular RNA regulation and function

Veronica F Busa; Anthony K L Leung

doi:10.1016/j.ymeth.2021.02.019

Thrown for a (stem) loop: How RNA structure impacts circular RNA regulation and function

Methods. 2021 Dec:196:56-67. doi: 10.1016/j.ymeth.2021.02.019. Epub 2021 Mar 2.

Authors

Veronica F Busa¹, Anthony K L Leung²

Affiliations

¹ McKusick-Nathans Institute of the Department of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; Department of Biochemistry and Molecular Biology, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD 21205, USA.
² McKusick-Nathans Institute of the Department of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; Department of Biochemistry and Molecular Biology, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD 21205, USA; Department of Molecular Biology and Genetics, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; Department of Oncology, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA. Electronic address: anthony.leung@jhu.edu.

PMID: 33662561
DOI: 10.1016/j.ymeth.2021.02.019

Abstract

Exonic circular RNAs (circRNAs) are RNA molecules that are covalently closed by back-splicing via canonical splicing machinery. Despite overlapping sequences, exon circularization generates RNA secondary structures through intramolecular base-pairing that are different from the linear transcript. Here we review factors that may affect circRNA structure and how structure affects circRNA function and regulation. We highlight considerations for RNA sequencing and expression measurement to ensure highly structured circRNAs are accurately represented by the data and discuss issues that need to be addressed in generating circRNAs to recapitulate their endogenous structures. We conclude our review by discussing experimental strategies on revealing the varied roles of RNA structure in circRNA biogenesis, function and decay.

Keywords: Circular RNA; RNA secondary structure.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Review

MeSH terms

Base Sequence
Exons
RNA Splicing / genetics
RNA* / genetics
RNA* / metabolism
RNA, Circular* / genetics

Substances

RNA, Circular
RNA

Grants and funding

T32 GM007814/GM/NIGMS NIH HHS/United States