Document Detail


Competition between small RNAs: a quantitative view.
MedLine Citation:
PMID:  22768926     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Two major classes of small regulatory RNAs--small interfering RNAs (siRNAs) and microRNA (miRNAs)--are involved in a common RNA interference processing pathway. Small RNAs within each of these families were found to compete for limiting amounts of shared components, required for their biogenesis and processing. Association with Argonaute (Ago), the catalytic component of the RNA silencing complex, was suggested as the central mechanistic point in RNA interference machinery competition. Aiming to better understand the competition between small RNAs in the cell, we present a mathematical model and characterize a range of specific cell and experimental parameters affecting the competition. We apply the model to competition between miRNAs and study the change in the expression level of their target genes under a variety of conditions. We show quantitatively that the amount of Ago and miRNAs in the cell are dominant factors contributing greatly to the competition. Interestingly, we observe what to our knowledge is a novel type of competition that takes place when Ago is abundant, by which miRNAs with shared targets compete over them. Furthermore, we use the model to examine different interaction mechanisms that might operate in establishing the miRNA-Ago complexes, mainly those related to their stability and recycling. Our model provides a mathematical framework for future studies of competition effects in regulation mechanisms involving small RNAs.
Authors:
Adiel Loinger; Yael Shemla; Itamar Simon; Hanah Margalit; Ofer Biham
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Biophysical journal     Volume:  102     ISSN:  1542-0086     ISO Abbreviation:  Biophys. J.     Publication Date:  2012 Apr 
Date Detail:
Created Date:  2012-07-09     Completed Date:  2012-10-09     Revised Date:  2013-07-12    
Medline Journal Info:
Nlm Unique ID:  0370626     Medline TA:  Biophys J     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1712-21     Citation Subset:  IM    
Copyright Information:
Copyright © 2012 Biophysical Society. Published by Elsevier Inc. All rights reserved.
Affiliation:
Racah Institute of Physics, The Hebrew University, Jerusalem, Israel.
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MeSH Terms
Descriptor/Qualifier:
Argonaute Proteins / metabolism
Binding, Competitive
Gene Expression Regulation
Humans
Kinetics
MicroRNAs / genetics*,  metabolism*
Models, Genetic*
RNA Stability
RNA, Messenger / chemistry,  genetics,  metabolism
RNA, Small Interfering / genetics*,  metabolism*
Chemical
Reg. No./Substance:
0/Argonaute Proteins; 0/MicroRNAs; 0/RNA, Messenger; 0/RNA, Small Interfering
Comments/Corrections

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