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Front. Genet. | doi: 10.3389/fgene.2018.00435

Target RNAs strike back on microRNAs

  • 1Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Argentina
  • 2CONICET Instituto de Fisiología, Biología Molecular y Neurociencias (IFIBYNE), Argentina
  • 3Instituto de Investigaciones Biotecnológicas (IIB-INTECH), Argentina

MicroRNAs are extensively studied regulatory non-coding small RNAs that silence animal genes throughout most biological processes, typically doing so by binding to partially complementary sequences within target RNAs. A plethora of studies has described detailed mechanisms for microRNA biogenesis and function, as well as their temporal and spatial regulation during development. By inducing translational repression and/or degradation of their target RNAs, microRNAs can contribute to achieve highly specific cell- or tissue-specific gene expression, while their aberrant expression can lead to disease. Yet an unresolved aspect of microRNA biology is how such small RNA molecules are themselves cleared from the cell, especially under circumstances where fast microRNA turnover or specific degradation of individual microRNAs are required. In recent years, it was unexpectedly found that binding of specific target RNAs to microRNAs with extensive complementarity can reverse the outcome, triggering degradation of the bound microRNAs. This emerging pathway, named TDMD for Target RNA-Directed MicroRNA Degradation, leads to microRNA 3’-end tailing by the addition of A/U non-templated nucleotides, trimming or shortening from the 3’ end, and highly specific microRNA loss, providing a new layer of microRNA regulation. Originally described in flies and known to be triggered by viral RNAs, novel endogenous instances of TDMD have been uncovered and are now starting to be understood. Here we review our current knowledge of this pathway and its potential role in the control and diversification of microRNA expression patterns.

Keywords: microRNA, degradation, tailing and trimming, uridylation, TDMD, Argonaute, exoribonuclease, terminal nucleotidyl transferase

Received: 01 Aug 2018; Accepted: 13 Sep 2018.

Edited by:

Hervé Seitz, Centre national de la recherche scientifique (CNRS), France

Reviewed by:

Alena Shkumatava, Institut Curie, France
Olivia Rissland, University of Colorado Denver, United States  

Copyright: © 2018 Fuchs Wightman, Giono, Fededa and de la Mata. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Dr. Manuel de la Mata, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Buenos Aires, Buenos Aires, Argentina, mmata@fbmc.fcen.uba.ar