MiRNA turnover control by linear and circular RNA targets

MANUEL DE LA MATA; MICHAEL B STADLER; MIRELA VITANESCU; HELGE GROßHANS; DIMOS GAIDATZIS; WITOLD FILIPOWICZ

Córdoba

Congreso; Reunión anual de la Sociedad Argentina de Investigación Bioquímica; 2016

Sociedad Argentina de Investigación Bioquímica

MicroRNAs(miRNAs) regulate target mRNAs by silencing them. Reciprocally, however, targetmRNAs can also modulate miRNA stability. We have shown that upon highlycomplementary binding, mRNAs trigger a remarkably effective Target RNA-directedmiRNA degradation (TDMD) in rodent primary neurons, greatly surpassing TDMD innon-neuronal cells and established cell lines. Although certain viruses employTDMD to degrade host miRNAs, some of which have antiviral activities, aphysiological function of TDMD remains to be identified. While TDMD may berelevant for miRNA regulation in the nervous system, the low naturalcomplementarity between miRNAs and their most commonly described target RNAs questionswhether normal endogenous targets physiologically trigger such regulation. CircularRNAs (circRNAs) have been recently shown to be particularly abundant in neuronsand, although their function remains enigmatic, some of them seem to interferewith miRNA activity. Here we explore circRNAs that regulate miRNA stability. Bymanipulating expression of endogenous circRNAs using lentiviral transgenes andCRISPR/Cas9 approaches, we analyse potential circular RNA species that might regulateTDMD in primary neurons.