Publication Date
4-12-2024
Journal
Nucleic Acids Research
DOI
10.1093/nar/gkae094
PMID
38381063
PMCID
PMC11014252
PubMedCentral® Posted Date
2-21-2024
PubMedCentral® Full Text Version
Post-print
Published Open-Access
yes
Keywords
MicroRNAs, RNA, RNA, Circular, RNA Stability, Humans, Animals, Mice
Abstract
A subset of circular RNAs (circRNAs) and linear RNAs have been proposed to 'sponge' or block microRNA activity. Additionally, certain RNAs induce microRNA destruction through the process of Target RNA-Directed MicroRNA Degradation (TDMD), but whether both linear and circular transcripts are equivalent in driving TDMD is unknown. Here, we studied whether circular/linear topology of endogenous and artificial RNA targets affects TDMD. Consistent with previous knowledge that Cdr1as (ciRS-7) circular RNA protects miR-7 from Cyrano-mediated TDMD, we demonstrate that depletion of Cdr1as reduces miR-7 abundance. In contrast, overexpression of an artificial linear version of Cdr1as drives miR-7 degradation. Using plasmids that express a circRNA with minimal co-expressed cognate linear RNA, we show differential effects on TDMD that cannot be attributed to the nucleotide sequence, as the TDMD properties of a sequence often differ when in a circular versus linear form. By analysing RNA sequencing data of a neuron differentiation system, we further detect potential effects of circRNAs on microRNA stability. Our results support the view that RNA circularity influences TDMD, either enhancing or inhibiting it on specific microRNAs.
Included in
Biochemistry, Biophysics, and Structural Biology Commons, Biology Commons, Medical Sciences Commons, Medical Specialties Commons
Comments
Associated Data