Competition between Small RNAs: A Quantitative View

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 p...

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Bibliographic Details
Published in:	Biophysical journal Vol. 102; no. 8; pp. 1712 - 1721
Main Authors:	Loinger, Adiel, Shemla, Yael, Simon, Itamar, Margalit, Hanah, Biham, Ofer
Format:	Journal Article
Language:	English
Published:	United States Elsevier Inc 18-04-2012 Biophysical Society The Biophysical Society
Subjects:	Argonaute Proteins - metabolism Binding, Competitive Biological Systems and Multicellular Dynamics Biophysics Biosynthesis Competition Gene expression Gene Expression Regulation Humans Kinetics Mathematical models MicroRNAs - genetics MicroRNAs - metabolism Models, Genetic Ribonucleic acid RNA RNA Stability RNA, Messenger - chemistry RNA, Messenger - genetics RNA, Messenger - metabolism RNA, Small Interfering - genetics RNA, Small Interfering - metabolism
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Summary:	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.
Bibliography:	ObjectType-Article-2 SourceType-Scholarly Journals-1 ObjectType-Feature-1 content type line 23 ObjectType-Article-1 ObjectType-Feature-2 Adiel Loinger and Yael Shemla contributed equally to this work.
ISSN:	0006-3495 1542-0086
DOI:	10.1016/j.bpj.2012.01.058