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An Argonaute 2 switch regulates circulating miR-210 to coordinate hypoxic adaptation across cells.

Authors
 Andrew Hale  ;  Changjin Lee  ;  Sofia Annis  ;  Pil-Ki Min  ;  Reena Pande  ;  Mark A. Creager  ;  Colleen G. Julian  ;  Lorna G. Moore  ;  S. Alex Mitsialis  ;  Sarah J. Hwang  ;  Stella Kourembanas  ;  Stephen Y. Chan 
Citation
 BIOCHIMICA ET BIOPHYSICA ACTA , Vol.1843(11) : 2528-2542, 2014 
Journal Title
 BIOCHIMICA ET BIOPHYSICA ACTA 
ISSN
 0006-3002 
Issue Date
2014
Keywords
Circulating microRNA ; Endothelial ; Hypoxamir ; Hypoxia ; Mitochondrial metabolism
Abstract
Complex organisms may coordinate molecular responses to hypoxia by specialized avenues of communication across multiple tissues, but these mechanisms are poorly understood. Plasma-based, extracellular microRNAs have been described, yet their regulation and biological functions in hypoxia remain enigmatic. We found a unique pattern of release of the hypoxia-inducible microRNA-210 (miR-210) from hypoxic and reoxygenated cells. This microRNA is also elevated in human plasma in physiologic and pathologic conditions of altered oxygen demand and delivery. Released miR-210 can be delivered to recipient cells, and the suppression of its direct target ISCU and mitochondrial metabolism is primarily evident in hypoxia. To regulate these hypoxia-specific actions, prolyl-hydroxylation of Argonaute 2 acts as a molecular switch that reciprocally modulates miR-210 release and intracellular activity in source cells as well as regulates intracellular activity in recipient cells after miR-210 delivery. Therefore, Argonaute 2-dependent control of released miR-210 represents a unique communication system that integrates the hypoxic response across anatomically distinct cells, preventing unnecessary activity of delivered miR-210 in normoxia while still preparing recipient tissues for incipient hypoxic stress and accelerating adaptation.
Full Text
http://www.sciencedirect.com/science/article/pii/S0167488914002158
DOI
10.1016/j.bbamcr.2014.06.012
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실) > 1. Journal Papers
Yonsei Authors
Min, Pil Ki(민필기) ORCID logo https://orcid.org/0000-0001-7033-7651
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/99831
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