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.

Degradation dynamics of micrornas revealed by a novel pulse-chase approach / M.J. Marzi, F. Ghini, B. Cerruti, S. De Pretis, P. Bonetti, C. Giacomelli, M.M. Gorski, T. Kress, M. Pelizzola, H. Muller, B. Amati, F. Nicassio. - In: GENOME RESEARCH. - ISSN 1088-9051. - 26:4(2016 Apr 26), pp. 554-565. [10.1101/gr.198788.115]

Degradation dynamics of micrornas revealed by a novel pulse-chase approach

F. Ghini
Primo
;
M.M. Gorski;
2016

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.
animals; argonaute proteins; fibroblasts; gene expression regulation; genome-wide association study; mice; micrornas; rna interference; rna stability; ribonuclease iii; time factors; transcription, genetic; genetics; genetics (clinical)
Settore BIO/11 - Biologia Molecolare
gen-2016
Article (author)
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2434/466487
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