RT Journal
A1 Marzi, Matteo J.
A1 Ghini, Francesco
A1 Cerruti, Benedetta
A1 de Pretis, Stefano
A1 Bonetti, Paola
A1 Giacomelli, Chiara
A1 Gorski, Marcin M.
A1 Kress, Theresia
A1 Pelizzola, Mattia
A1 Muller, Heiko
A1 Amati, Bruno
A1 Nicassio, Francesco
T1 Degradation dynamics of microRNAs revealed by a novel pulse-chase approach
JF Genome Research 
JO Genome Research 
YR 2016 
FD April 01 
VO 26 
IS 4 
SP 554 
OP 565 
DO 10.1101/gr.198788.115 
UL http://genome.cshlp.org/content/26/4/554.abstract 
AB 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.