Target-mediated microRNA decay in neurons

DE LA MATA M., VITANESCU M., GAIDATZIS D. , FILIPOWICZ W., GROSSHANS H.

Seattle

Simposio; Keystone symposium on RNA Silencing; 2014

Keystone Symposia

Although known for their functions in controlling mRNAs, it is becoming increasingly clear that miRNAs themselves are subject to extensive regulation, including at the level of their degradation. MiRNAs typically function by accelerating deadenylation and degradation of target mRNAs. Conversely, it has been shown that target mRNAs or non-coding RNAs can reciprocally induce decay of miRNAs associated with them. We find that target mRNAs efficiently trigger decay of miRNAs in rodent hippocampal neurons in a manner that depends on the target-miRNA stoichiometry, binding site architecture, and on the identity of the miRNA. Target-mediated miRNA decay (TMMD) appears to be much stronger in primary hippocampal neurons than in other cells such as HEK-293T and SH-SY5Y neuroblastoma cell lines. Early after target induction, cognate miRNAs undergo multiple non-templated nucleotide additions with mainly U- and A-tails being generated in several combinations. The different tailed species follow different kinetics after target induction, potentially mediating early stages of the degradation pathway. We propose that the high efficiency of TMMD observed in neurons might be the consequence of a mechanism involving multiple turnover activity.