Potent target-mediated miRNA decay in neurons

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

Heidelberg

Simposio; EMBO|EMBL Symposium The Complex Life of mRNA; 2014

European Molecular Biology Laboratory (EMBL).

MicroRNAs (miRNAs) regulate target mRNAs by silencing them. Reciprocally, however, target mRNAs can also modulate miRNA stability. Here, we uncover a remarkable efficacy of target RNA-directed miRNA degradation (TDMD) in rodent primary neurons. Coincident with degradation, and while still bound to Argonaute, targeted miRNAs are 3´ terminally tailed and trimmed. Absolute quantification of both miRNAs and their decay-inducing targets suggests that neuronal TDMD is multiple turnover, and does not involve co-degradation of the target but rather competes with miRNA-mediated decay of the target. This knowledge can be harnessed for effective depletion of abundant miRNAs. Our findings bring insight into a potent miRNA degradation pathway in primary neurons, whose TDMD activity greatly surpasses that of non-neuronal cells and established cell lines. Thus, TDMD may be particularly relevant for miRNA regulation in the nervous system.