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 Repjournal_title
EMBO reportsauthors
de la Mata M,Gaidatzis D,Vitanescu M,Stadler MB,Wentzel C,Scheiffele P,Filipowicz W,Großhans Hdoi
10.15252/embr.201540078subject
Has Abstractpub_date
2015-04-01 00:00:00pages
500-11issue
4eissn
1469-221Xissn
1469-3178pii
embr.201540078journal_volume
16pub_type
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