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1. chinaXiv:201605.01003 [pdf]

Theoretical Analysis of Catalytic-sRNA-Mediated Gene Silencing

Yue Hao; fangliu xu; hualin shi
Subjects: Physics >> Interdisciplinary Physics and Related Areas of Science and Technology

Small regulatory RNA (sRNA) that acts by an antisense mechanism is critical for gene regulation at the posttranscriptional level. Recently, an Hfq-dependent sRNA named MicM, which is related to the regulation of outer membrane protein, was verified as a novel antisense sRNA due to its catalytic mode of regulation. Here we propose a simple kinetic model for the enzyme-like regulation mode of sRNA and study in detail the noise properties of the target gene under various recycling rates of the regulator. We predict that the recycling rate of sRNA and other relative parameters have significant influence on the noise strength of target expression. In comparison with the stoichiometric regulatory mode, a lesser fluctuation of target expression was observed near the threshold at which the transcription rates of both sRNA and target mRNA equal each other. We also found that the new mode is better in terms of rapid response to external signals. However, it needs more time to achieve target recovery if the stimulating signal disappears. Additionally, the obtained time evolution results of the MicM-ybfM interaction system based on our model are consistent with previous experimental results, serving as experimental evidence to back up our theoretical analysis. (C) 2010 Elsevier Ltd. All rights reserved.

submitted time 2016-05-08 Hits1546Downloads599 Comment 0

2. chinaXiv:201605.00998 [pdf]

Quantifying the sequence-function relation in gene silencing by bacterial small RNAs

Yue Hao; Zhongge J. Zhang; David W. Erickson; Min Huang; Yingwu Huang; Junbai Li; Terence Hwa; hualin shi
Subjects: Physics >> Interdisciplinary Physics and Related Areas of Science and Technology

Sequence-function?relations for?small?RNA (sRNA)-mediated?gene?silencing?were quantified for?the?sRNA RyhB and some of its mRNA targets?in?Escherichia coli. Numerous mutants of RyhB and its targets were generated and their?in?vivo functions characterized at various levels of target and RyhB expression. Although a core complementary region is required for repression?by?RyhB, variations?in?the?complementary sequences of?the?core region gave rise to a continuum of repression strengths, correlated exponentially with?the?computed free energy of RyhB-target duplex formation. Moreover,?sequence?variations?inthe?linker region known to interact with?the?RNA chaperone Hfq also gave rise to a continuum of repression strengths, correlated exponentially with?thecomputed energy cost of keeping?the?linker region open. These results support?the?applicability of?the?thermodynamic model?in?predicting sRNA-mRNA interaction and suggest that sequences at these locations may be used to fine-tune?the?degree of repression. Surprisingly, a truncated RyhB without?the?Hfq-binding region is found to repress multiple targets of?the?wild-type RyhB effectively, both?in?the?presence and absence of Hfq, even though?the?former is required for?the?activity of wild-type RyhB itself. These findings challenge?the?commonly accepted model concerning?the?function?of Hfq?in?gene?silencing-bothin?providing stability to?the?sRNAs and?in?catalyzing?the?target mRNAs to take on active conformations-and raise?the?intriguing question of why many endogenous sRNAs subject their functions to Hfq-dependences.

submitted time 2016-05-08 Hits1514Downloads542 Comment 0

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