Bifurcation and Oscillatory Dynamics of Delayed Cyclic Gene Networks Including Small RNAs

AbstractMicroRNAs (miRNA) are small RNAs that function as key modulators of gene expression. Due to their promiscuity of binding, a single miRNA may regulate several genes and hence, multiple pathways simultaneously. In addition, the 3’-UTR of mRNA can be recognized by several miRNA for suppression or degradation. We built a microRNA-only Knock-out (miRKo) CRISPR/Cas-9 library to identify essential miRNA in Acute Myeloid Leukemia (AML) using OCI-AML2, OCI-AML3 and U937 cell lines as in vitro models. 10 miRNA were identified to be essential in our screen among all three cell lines: miR-19b-1, -19b-2, 29b-2, -302a, -3678, -3713, -3910-1, -4447, -4718 and -6795. By using weighted degrees of association, we identified pathway hubs that uniquely affect all 3 cell lines by integrating miRNA:mRNA networks using mirDIP and pathway analysis using pathDIP. Through the miRKo screen, network membership analyses and biological anticorrelation scoring through patient data analysis, we identified RRP2CA, RPS6KB-1, CREB1, RPM1A, MAPK10, MAP3K2, ITCH, FBX-W7, NR3C1 and XIAP as likely targets of the essential miRNA in AML; and signal transduction, apoptosis, TGF-beta signalling and MAPK signalling as candidate essential pathways in AML.

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Buffering in cyclic gene networks

Theoretical and Mathematical Physics ◽

10.1134/s0040577916060106 ◽

2016 ◽

Vol 187 (3) ◽

pp. 935-951

Author(s):

S. D. Glyzin ◽

A. Yu. Kolesov ◽

N. Kh. Rozov

Keyword(s):

Gene Networks ◽

Cyclic Gene

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Vertebrate Segmentation: From Cyclic Gene Networks to Scoliosis

Cell ◽

10.1016/j.cell.2011.05.011 ◽

2011 ◽

Vol 145 (5) ◽

pp. 650-663 ◽

Cited By ~ 210

Author(s):

Olivier Pourquié

Keyword(s):

Gene Networks ◽

Cyclic Gene

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Post-transcriptional regulation of cellulose synthase genes by small RNAs derived from CESA antisense transcripts

10.1101/2020.04.30.070854 ◽

2020 ◽

Author(s):

Daniel B. Nething ◽

John W. Mishler-Elmore ◽

Michael A. Held

Keyword(s):

Cell Wall ◽

Small Rnas ◽

Gene Networks ◽

Plant Cell Wall ◽

Brachypodium Distachyon ◽

Primary Cell Wall ◽

Cell Wall Biosynthesis ◽

Antisense Transcripts ◽

Transcriptional Regulatory ◽

Transcriptional Regulatory Mechanisms

AbstractTranscriptional regulatory mechanisms governing plant cell wall biosynthesis are incomplete. Expression programs that activate wall biosynthesis are well understood, but mechanisms that control the attenuation of gene expression networks remain elusive. Previous work has shown that small RNAs (sRNAs) derived from the HvCESA6 (Hordeum vulgare, Hv) antisense transcripts are naturally produced and are capable of regulating aspects of wall biosynthesis. Here, we further test the hypothesis that CESA-derived sRNAs generated from CESA antisense transcripts are involved in the regulation of cellulose and broader cell wall biosynthesis. Antisense transcripts were detected for some, but not all members of the CESA gene family in both barley and Brachypodium distachyon. Phylogenetic analysis indicates that antisense transcripts are detected for most primary cell wall CESA genes, suggesting a possible role in the transition from primary to secondary cell wall biosynthesis. Focusing on one antisense transcript, HvCESA1 shows dynamic expression throughout development, is correlated with corresponding sRNAs over the same period and is anticorrelated with HvCESA1 mRNA expression. To assess the broader impacts of CESA-derived sRNAs on the regulation of cell wall biosynthesis, transcript profiling was performed on barley tissues overexpressing CESA-derived sRNAs. Together the data support the hypothesis that CESA antisense transcripts function, through an RNA-induced silencing mechanism, to degrade cis transcripts, and may also trigger trans-acting silencing on related genes to alter the expression of cell wall gene networks.

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