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Small RNA driven feed-forward loop: critical role of sRNA in noise filtering.

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Relation http://ir.cftri.com/14201/
https://dx.doi.org/10.1088/1478-3975/ab1563
 
Title Small RNA driven feed-forward loop: critical role of sRNA in noise
filtering.
 
Creator Swathi, Tej
Gaurav, Kumar
Sutapa, Mukherji
 
Subject 03 Biochemistry & Molecular Biology
 
Description Gene regulatory networks are often partitioned into di�erent types of recurring network motifs.
A feed-forward loop (FFL) is a common motif in which an upstream regulator is a protein, typically
a transcription factor, that regulates the expression of the target protein in two ways - �rst, directly
by regulating the mRNA levels of the target protein and second, indirectly via an intermediate
molecule that in turn regulates the target protein level. Investigations on two variants of FFL -
purely transcriptional FFL (tFFL) and sRNA-mediated FFL (smFFL) reveal several advantages of
using such motifs. Here, we study a distinct sRNA-driven FFL (sFFL) that was discovered recently
in Salmonella enterica: The distinction being the upstream regulator here is not a protein but
an sRNA that translationally activates the target protein expression directly; and also indirectly
via regulation of the transcriptional activator of the target protein. This variant, i.e. sFFL has
not been subjected to rigorous analysis. We therefore set out to understand two aspects. First
is a quantitative comparison of the regulatory response of sFFL with tFFL and smFFL using a
di�erential equation framework. Since, the process of gene expression is inherently stochastic, the
second objective is to �nd how noise in gene expression a�ects the functionality of the sFFL. We
�nd that unlike for tFFL and smFFL, the response of sFFL is stronger and faster: the change in
target protein concentration is rapid and depends critically on the initial concentration of sRNA.
Further, our analysis based on generating function approach and stochastic simulations leads to a
non-trivial prediction that an optimal noise �ltration can be attained depending on the synthesis
rate of the upstream sRNA and the degradation rate of the intermediate transcriptional activator.
A comparison with a simpler process involving only translational activation by sRNA indicates that
the design of sFFL is crucial for optimal noise �ltration. These observations prompt us to conclude
that sFFL has distinct advantages where the master regulator, sRNA, plays a critical role not only
in driving a rapid and strong response, but also a reliable response that depends critically on its
concentration.
 
Date 2019
 
Type Article
PeerReviewed
 
Format pdf
 
Language en
 
Identifier http://ir.cftri.com/14201/1/Phys.%20Biol%202019.pdf
Swathi, Tej and Gaurav, Kumar and Sutapa, Mukherji (2019) Small RNA driven feed-forward loop: critical role of sRNA in noise filtering. Physical Biology, 64 (4). pp. 1-17.