Degradation dynamics of microRNAs revealed by a novel pulse-chase approach
- Matteo J. Marzi1,3,
- Francesco Ghini1,3,
- Benedetta Cerruti1,
- Stefano de Pretis1,
- Paola Bonetti1,
- Chiara Giacomelli1,
- Marcin M. Gorski2,
- Theresia Kress1,2,
- Mattia Pelizzola1,
- Heiko Muller1,
- Bruno Amati1,2 and
- Francesco Nicassio1
- 1Center for Genomic Science of IIT@SEMM, Istituto Italiano di Tecnologia (IIT), 20139 Milan, Italy;
- 2Department of Experimental Oncology, European Institute of Oncology (IEO), 20139 Milan, Italy
- Corresponding authors: matteo.marzi{at}iit.it, francesco.nicassio{at}iit.it
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↵3 These authors contributed equally to this work.
Abstract
The regulation of miRNAs is critical to the definition of cell identity and behavior in normal physiology and disease. To date, the dynamics of miRNA degradation and the mechanisms involved in remain largely obscure, in particular, in higher organisms. Here, we developed a pulse-chase approach based on metabolic RNA labeling to calculate miRNA decay rates at genome-wide scale in mammalian cells. Our analysis revealed heterogeneous miRNA half-lives, with many species behaving as stable molecules (T1/2 > 24 h), while others, including passenger miRNAs and a number (25/129) of guide miRNAs, are quickly turned over (T1/2 = 4–14 h). Decay rates were coupled with other features, including genomic organization, transcription rates, structural heterogeneity (isomiRs), and target abundance, measured through quantitative experimental approaches. This comprehensive analysis highlighted functional mechanisms that mediate miRNA degradation, as well as the importance of decay dynamics in the regulation of the miRNA pool under both steady-state conditions and during cell transitions.
Footnotes
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[Supplemental material is available for this article.]
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Article published online before print. Article, supplemental material, and publication date are at http://www.genome.org/cgi/doi/10.1101/gr.198788.115.
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Freely available online through the Genome Research Open Access option.
- Received August 31, 2015.
- Accepted January 19, 2016.
This article, published in Genome Research, is available under a Creative Commons License (Attribution-NonCommercial 4.0 International), as described at http://creativecommons.org/licenses/by-nc/4.0/.
