Format

Send to

Choose Destination
Cell Mol Life Sci. 2018 Mar;75(6):1071-1098. doi: 10.1007/s00018-017-2688-5. Epub 2017 Nov 7.

Molecular roles and function of circular RNAs in eukaryotic cells.

Author information

1
Institute of Laboratory Medicine, University Hospital, LMU Munich, Marchioninistr. 15, 81377, Munich, Germany. Lesca.Holdt@med.uni-muenchen.de.
2
Institute of Laboratory Medicine, University Hospital, LMU Munich, Marchioninistr. 15, 81377, Munich, Germany.
3
Faculty of Biology, Genetics, LMU Munich, Großhaderner Str. 2-4, 82152, Martinsried, Germany.

Abstract

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.

KEYWORDS:

Alu elements; Cancer; Cardiovascular disease; Chromatin; Exosomes; RNA polymerase II; Spliceosome; microRNA

PMID:
29116363
PMCID:
PMC5814467
DOI:
10.1007/s00018-017-2688-5
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Springer Icon for PubMed Central
Loading ...
Support Center