Journal Article

Molecular roles and function of circular RNAs in eukaryotic cells

Kohlmaier, Alexander, Holdt, Lesca M., Teupser, Daniel

2018

Overview

Protein-coding and noncoding genes in eukaryotes are typically expressed as linear messenger RNAs, with exons arranged colinearly to their genomic order. Recent advances in sequencing and in mapping RNA reads to reference genomes have revealed that thousands of genes express also covalently closed circular RNAs. Many of these circRNAs are stable and contain exons, but are not translated into proteins. Here, we review the emerging understanding that both, circRNAs produced by co- and posttranscriptional head-to-tail “backsplicing” of a downstream splice donor to a more upstream splice acceptor, as well as circRNAs generated from intronic lariats during colinear splicing, may exhibit physiologically relevant regulatory functions in eukaryotes. We describe how circRNAs impact gene expression of their host gene locus by affecting transcriptional initiation and elongation or splicing, and how they partake in controlling the function of other molecules, for example by interacting with microRNAs and proteins. We conclude with an outlook how circRNA dysregulation affects disease, and how the stability of circRNAs might be exploited in biomedical applications.

• Publisher: Springer International Publishing,Springer Nature B.V
• Subject: Alternative Splicing / Alu Elements / Biochemistry / Biomedical and Life Sciences / Biomedical materials / Biomedicine / Cardiovascular Diseases - genetics / Cardiovascular Diseases - metabolism / Cardiovascular Diseases - pathology / Cell Biology / Cells / chemical bonding / Chromatin - chemistry / Chromatin - metabolism / Circular RNA / Elongation / Eukaryotes / eukaryotic cells / Eukaryotic Cells - cytology / Eukaryotic Cells - metabolism / Exons / Gene expression / Gene mapping / Gene sequencing / Genes / Genomes / genomics / Humans / Introns / Life Sciences / loci / messenger RNA / microRNA / MicroRNAs - genetics / MicroRNAs - metabolism / miRNA / Molecular biology / Neoplasms - genetics / Neoplasms - metabolism / Neoplasms - pathology / Post-transcription / Proteins / Review / Ribonucleic acid / RNA / RNA - genetics / RNA - metabolism / RNA Polymerase II - genetics / RNA Polymerase II - metabolism / RNA Stability / RNA, Circular / RNA, Messenger - genetics / RNA, Messenger - metabolism / Spliceosomes - genetics / Spliceosomes - metabolism / Splicing / Trans-Splicing / transcription (genetics) / Transcription elongation / Transcription initiation / translation (genetics)