Potent degradation of neuronal miRNAs induced by highly complementary targets.

Abstract:

: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. Moreover, mRNA silencing, but not TDMD, relies on cooperativity among multiple target sites to reach high efficacy. 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.

journal_name

EMBO Rep

journal_title

EMBO reports

authors

de la Mata M,Gaidatzis D,Vitanescu M,Stadler MB,Wentzel C,Scheiffele P,Filipowicz W,Großhans H

doi

10.15252/embr.201540078

subject

Has Abstract

pub_date

2015-04-01 00:00:00

pages

500-11

issue

4

eissn

1469-221X

issn

1469-3178

pii

embr.201540078

journal_volume

16

pub_type

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