Small regulatory RNAs may sharpen spatial expression patterns.

The precise establishment of gene expression patterns is a crucial step in development. Formation of a sharp boundary between high and low spatial expression domains requires a genetic mechanism that exhibits sensitivity, yet is robust to fluctuations, a demand that may not be easily achieved by mor...

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Main Authors: Erel Levine, Peter McHale, Herbert Levine
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2007-11-01
Series:PLoS Computational Biology
Online Access:http://europepmc.org/articles/PMC2098861?pdf=render
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author Erel Levine
Peter McHale
Herbert Levine
author_facet Erel Levine
Peter McHale
Herbert Levine
author_sort Erel Levine
collection DOAJ
description The precise establishment of gene expression patterns is a crucial step in development. Formation of a sharp boundary between high and low spatial expression domains requires a genetic mechanism that exhibits sensitivity, yet is robust to fluctuations, a demand that may not be easily achieved by morphogens alone. Recently, it has been demonstrated that small RNAs (and, in particular, microRNAs) play many roles in embryonic development. Whereas some RNAs are essential for embryogenesis, others are limited to fine-tuning a predetermined gene expression pattern. Here, we explore the possibility that small RNAs participate in sharpening a gene expression profile that was crudely established by a morphogen. To this end, we study a model in which small RNAs interact with a target gene and diffusively move from cell to cell. Though diffusion generally smoothens spatial expression patterns, we find that intercellular mobility of small RNAs is actually critical in sharpening the interface between target expression domains in a robust manner. This sharpening occurs as small RNAs diffuse into regions of low mRNA expression and eliminate target molecules therein, but cannot affect regions of high mRNA levels. We discuss the applicability of our results, as examples, to the case of leaf polarity establishment in maize and Hox patterning in the early Drosophila embryo. Our findings point out the functional significance of some mechanistic properties, such as mobility of small RNAs and the irreversibility of their interactions. These properties are yet to be established directly for most classes of small RNAs. An indirect yet simple experimental test of the proposed mechanism is suggested in some detail.
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spelling doaj.art-0c7d241ca888457786b9e77961faf7522022-12-21T19:21:12ZengPublic Library of Science (PLoS)PLoS Computational Biology1553-734X1553-73582007-11-01311e23310.1371/journal.pcbi.0030233Small regulatory RNAs may sharpen spatial expression patterns.Erel LevinePeter McHaleHerbert LevineThe precise establishment of gene expression patterns is a crucial step in development. Formation of a sharp boundary between high and low spatial expression domains requires a genetic mechanism that exhibits sensitivity, yet is robust to fluctuations, a demand that may not be easily achieved by morphogens alone. Recently, it has been demonstrated that small RNAs (and, in particular, microRNAs) play many roles in embryonic development. Whereas some RNAs are essential for embryogenesis, others are limited to fine-tuning a predetermined gene expression pattern. Here, we explore the possibility that small RNAs participate in sharpening a gene expression profile that was crudely established by a morphogen. To this end, we study a model in which small RNAs interact with a target gene and diffusively move from cell to cell. Though diffusion generally smoothens spatial expression patterns, we find that intercellular mobility of small RNAs is actually critical in sharpening the interface between target expression domains in a robust manner. This sharpening occurs as small RNAs diffuse into regions of low mRNA expression and eliminate target molecules therein, but cannot affect regions of high mRNA levels. We discuss the applicability of our results, as examples, to the case of leaf polarity establishment in maize and Hox patterning in the early Drosophila embryo. Our findings point out the functional significance of some mechanistic properties, such as mobility of small RNAs and the irreversibility of their interactions. These properties are yet to be established directly for most classes of small RNAs. An indirect yet simple experimental test of the proposed mechanism is suggested in some detail.http://europepmc.org/articles/PMC2098861?pdf=render
spellingShingle Erel Levine
Peter McHale
Herbert Levine
Small regulatory RNAs may sharpen spatial expression patterns.
PLoS Computational Biology
title Small regulatory RNAs may sharpen spatial expression patterns.
title_full Small regulatory RNAs may sharpen spatial expression patterns.
title_fullStr Small regulatory RNAs may sharpen spatial expression patterns.
title_full_unstemmed Small regulatory RNAs may sharpen spatial expression patterns.
title_short Small regulatory RNAs may sharpen spatial expression patterns.
title_sort small regulatory rnas may sharpen spatial expression patterns
url http://europepmc.org/articles/PMC2098861?pdf=render
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