scholarly journals A modular RNA interference system for multiplexed gene regulation

2019 ◽  
Author(s):  
Ari Dwijayanti ◽  
Marko Storch ◽  
Guy-Bart Stan ◽  
Geoff S. Baldwin
Keyword(s):  
Transcriptional Regulation ◽  
Genetic Control ◽  
Rational Design ◽  
Single Gene ◽  
Regulation Of Gene Expression ◽  
Genetic Circuit ◽  
Regulatory Function ◽  
Dna Assembly ◽  
Strain Type ◽  
Post Transcriptional Regulation

ABSTRACTThe rational design and realization of simple-to-use genetic control elements that are modular, orthogonal and robust is essential to the construction of predictable and reliable biological systems of increasing complexity. To this effect, we introduce modular Artificial RNA interference (mARi), a rational, modular and extensible design framework that enables robust, portable and multiplexed post-transcriptional regulation of gene expression in Escherichia coli. The regulatory function of mARi was characterized in a range of relevant genetic and cellular contexts and was shown to be independent of other genetic control elements and the gene of interest, as well as growth-phase and strain type. Importantly, the extensibility and orthogonality of mARi enables the simultaneous post-transcriptional regulation of multi-gene systems as both single-gene cassettes and poly-cistronic operons. To facilitate adoption, mARi was designed to be directly integrated into the modular BASIC DNA assembly framework. We anticipate that mARi-based genetic control within an extensible DNA assembly framework will facilitate metabolic engineering, layered genetic control, and advanced genetic circuit applications.

scholarly journals Antagonistic roles of NOT1 paralogues in the timing of gene expression in Plasmodium falciparum

2020 ◽  
Author(s):  
Ying Liu ◽  
Ragini Rai ◽  
Lei Zhu ◽  
Changqing Zhang ◽  
Frances Rocamora ◽  
...  
Keyword(s):  
Gene Expression ◽  
Gene Regulation ◽  
Plasmodium Falciparum ◽  
Transcriptional Regulation ◽  
Protein Complex ◽  
Single Gene ◽  
Regulatory Function ◽  
Developmental Cycle ◽  
Regulatory Functions ◽  
Post Transcriptional Regulation

AbstractNOT1 is the scaffold of the CCR4-NOT complex, a highly conserved multi-protein complex that regulates gene expression in eukaryotes. As opposed to most eukaryotes in which NO1 is encoded by a single gene, malaria parasites, Plasmodium falciparum, carry two NOT1 paralogues, PfNOT1.1 and PfNOT1.2. Here we showed that the two PfNOT1 proteins function as mutually exclusive scaffolds within the PfCCR4-NOT protein complexes that are abundantly located in the parasite cytoplasm. Intriguingly, the two PfNOT1 paralogues appear to have directly opposing functions in regulation of mRNA abundance across the P. falciparum IDC, in which PfNTO1.1 and PfNOT1.2 induces and suppresses transcript abundance during their active transcription, respectively. Targeted disruption of either of the PfNOT1 gene causes defective growth and lower invasion rates presumably due to the deregulation the P. falciparum IDC transcriptional cascade. We also demonstrate that the regulatory function of both PfNOT1.1 and PfNOT1.2 are related to another PfCCR4-NOT subunit, PfCaf1, which indicates their activity during post-transcriptional regulation. Indeed RNA decay studies suggest the active role of both PfNOT1 proteins in regulation of mRNA stability in a directly opposing manner.Author summaryCCR4-NOT complex is a highly conserved multi-protein complex that regulates gene expression in eukaryotes. NOT1 serves as the scaffold of the complex and plays important roles in gene regulation both transcriptionally and post-transcriptionally. As opposed to other eukaryotes, P. falciparum encodes two paralogues of PfNOT1, raising the question as to the significance to possess an additional copy of PfNOT1 in the parasite. Here we described antagonistic regulatory functions of two PfNOT1 paralogues in gene expression during the 48-hour intraerythrocytic developmental cycle. We also reported that their regulatory functions are predominantly post-transcriptional and proposed a model in which distinct PfCCR4-NOT complexes defined by mutually exclusive PfNOT1 scaffolds differentially regulate PfCAF1 function in mRNA decay. This study highlights the importance of post-transcriptional regulation in P. falciparum and provides novel insights into mechanisms of gene regulation in this organism. The unique presence of two PfNOT1 paralogues may also open avenues for the development of new drug targets for anti-malarial control.

Post-transcriptional regulation of gene expression

Methods ◽  
2017 ◽  
Vol 126 ◽  
pp. 1-2 ◽  
Author(s):  
Howard D. Lipshitz ◽  
Julie M. Claycomb ◽  
Craig A. Smibert
Keyword(s):  
Gene Expression ◽  
Transcriptional Regulation ◽  
Regulation Of Gene Expression ◽  
Post Transcriptional Regulation

scholarly journals Post-transcriptional regulation of gene expression by degradation of messenger RNAs

2003 ◽  
Vol 195 (3) ◽  
pp. 356-372 ◽  
Author(s):  
Annamaria Bevilacqua ◽  
Maria Cristina Ceriani ◽  
Sergio Capaccioli ◽  
Angelo Nicolin
Keyword(s):  
Gene Expression ◽  
Transcriptional Regulation ◽  
Regulation Of Gene Expression ◽  
Messenger Rnas ◽  
Post Transcriptional Regulation

scholarly journals Regulatory signals in messenger RNA: determinants of nutrient–gene interaction and metabolic compartmentation

1998 ◽  
Vol 80 (4) ◽  
pp. 307-321
Author(s):  
John E. Hesketh ◽  
M. Helena Vasconcelos ◽  
Giovanna Bermano
Keyword(s):  
Gene Expression ◽  
Transcriptional Regulation ◽  
Mrna Stability ◽  
Transcriptional Control ◽  
Regulation Of Gene Expression ◽  
Untranslated Regions ◽  
Nutritional Requirements ◽  
Control Of Gene Expression ◽  
Metabolic Compartmentation ◽  
Post Transcriptional Regulation

Nutrition has marked influences on gene expression and an understanding of the interaction between nutrients and gene expression is important in order to provide a basis for determining the nutritional requirements on an individual basis. The effects of nutrition can be exerted at many stages between transcription of the genetic sequence and production of a functional protein. This review focuses on the role of post-transcriptional control, particularly mRNA stability, translation and localization, in the interactions of nutrients with gene expression. The effects of both macronutrients and micronutrients on regulation of gene expression by post-transcriptional mechanisms are presented and the post-transcriptional regulation of specific genes of nutritional relevance (glucose transporters, transferrin, selenoenzymes, metallothionein, lipoproteins) is described in detail. The function of the regulatory signals in the untranslated regions of the mRNA is highlighted in relation to control of mRNA stability, translation and localization and the importance of these mRNA regions to regulation by nutrients is illustrated by reference to specific examples. The localization of mRNA by signals in the untranslated regions and its function in the spatial organization of protein synthesis is described; the potential of such mechanisms to play a key part in nutrient channelling and metabolic compartmentation is discussed. It is concluded that nutrients can influence gene expression through control of the regulatory signals in these untranslated regions and that the post-transcriptional regulation of gene expression by these mechanisms may influence nutritional requirements. It is emphasized that in studies of nutritional control of gene expression it is important not to focus only on regulation through gene promoters but also to consider the possibility of post-transcriptional control.

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