Work

Mammalian circular RNAs result largely from splicing errors

Year: 2021

Type: article

Abstract: Ubiquitous in eukaryotes, circular RNAs (circRNAs) comprise a large class of mostly non-coding RNAs produced by back-splicing. Although some circRNAs have demonstrated biochemical activities, whether most circRNAs are functional is unknown. Here, we test the hypothesis that circRNA production primarily results from splicing error and so is deleterious instead of beneficial. In support of the error hypothesis, our analysis of RNA sequencing data from 11 shared tissues of humans, macaques, and mice finds that (1) back-splicing is much rarer than linear-splicing, (2) the rate of back-splicing diminishes with the splicing amount, (3) the overall prevalence of back-splicing in a species declines with its effective population size, and (4) circRNAs are overall evolutionarily unconserved. We estimate that more than 97% of the observed circRNA production is deleterious. We identify a small number of functional circRNA candidates, and the genome-wide trend strongly suggests that circRNAs are largely non-functional products of splicing errors.

Source: Cell Reports

DOI: 10.1016/j.celrep.2021.109439

Authors: Chuan Xu, Jianzhi Zhang

Institutions: Shanghai Jiao Tong University, University of Michigan

Language: English

Topic: Circular RNAs in diseases

Subfield: Molecular Biology

Field: Biochemistry, Genetics and Molecular Biology

Domain: Life Sciences

Open Access status: gold

Estimated APC paid: $5,200

Funders: National Institutes of Health, National Institute of General Medical Sciences