Potent degradation of neuronal miRNAs induced by highly complementary targets

de la Mata, Manuel and Gaidatzis, Dimos and Vitanescu, Mirela and Stadler, Michael B. and Wentzel, Corinna and Scheiffele, Peter and Filipowicz, Witold and Großhans, Helge. (2015) Potent degradation of neuronal miRNAs induced by highly complementary targets. EMBO reports, Vol. 16, H. 4. pp. 500-511.

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Official URL: http://edoc.unibas.ch/dok/A6420007

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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.
Faculties and Departments:05 Faculty of Science > Departement Biozentrum > Neurobiology > Cell Biology (Scheiffele)
UniBasel Contributors:Scheiffele, Peter
Item Type:Article, refereed
Article Subtype:Research Article
Publisher:Nature Publishing Group
Note:Publication type according to Uni Basel Research Database: Journal article
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Last Modified:02 Oct 2015 10:00
Deposited On:02 Oct 2015 10:00

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