Influence of RNA circularity on Target RNA-Directed MicroRNA Degradation

WIGHTMAN FF; LUKIN J; GIUSTI SA; SOUTSCHEK M; BRAGADO L; POZZI B; PIERELLI ML; GONZÁLEZ P; FEDEDA JP; SCHRATT G; FUJIWARA R; WILUSZ JE; REFOJO D,; DE LA MATA M,

Nucleic Acid Research

Oxford University Press

Año: 2024

1362-4962

A subset of circular RNAs (circRNAs) and linear RNAs ha v e 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 pre vious kno wledge 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, o v ere xpression of an artificial linear version of Cdr1as drives miR-7 degradation. Using plasmids that express a circRNA with minimal co-expressed cognate linear RNA, w e sho w 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 st abilit y. Our results support the view that RNA circularity influences TDMD, either enhancing or inhibiting it on specific microRNAs.