scholarly journals Suppression of Gene Expression by Targeted Disruption of Messenger RNA: Available Options and Current Strategies

Stem Cells ◽  
2000 ◽  
Vol 18 (5) ◽  
pp. 307-319 ◽  
Author(s):  
Kuang-Yu Jen ◽  
Alan M. Gewirtz
2017 ◽  
Vol 2 (1) ◽  
Author(s):  
Vijayalakshmi H Nagaraj ◽  
James M Greene ◽  
Anirvan M Sengupta ◽  
Eduardo D Sontag

Abstract Quantifying the effect of vital resources on transcription (TX) and translation (TL) helps to understand the degree to which the concentration of each resource must be regulated for achieving homeostasis. Utilizing the synthetic TX-TL system, we study the impact of nucleotide triphosphates (NTPs) and magnesium (Mg2+) on gene expression. Recent observations of the counter-intuitive phenomenon of suppression of gene expression at high NTP concentrations have led to the speculation that such suppression is due to the consumption of resources by TX, hence leaving fewer resources for TL. In this work, we investigate an alternative hypothesis: direct suppression of the TL rate via stoichiometric mismatch in necessary reagents. We observe NTP-dependent suppression even in the early phase of gene expression, contradicting the resource-limitation argument. To further decouple the contributions of TX and TL, we performed gene expression experiments with purified messenger RNA (mRNA). Simultaneously monitoring mRNA and protein abundances allowed us to extract a time-dependent translation rate. Measuring TL rates for different Mg2+ and NTP concentrations, we observe a complex resource dependence. We demonstrate that TL is the rate-limiting process that is directly inhibited by high NTP concentrations. Additional Mg2+ can partially reverse this inhibition. In several experiments, we observe two maxima of the TL rate viewed as a function of both Mg2+ and NTP concentration, which can be explained in terms of an NTP-independent effect on the ribosome complex and an NTP-Mg2+ titration effect. The non-trivial compensatory effects of abundance of different vital resources signal the presence of complex regulatory mechanisms to achieve optimal gene expression.


Author(s):  
Matthias Fladung ◽  
Hely Häggman ◽  
Suvi Sutela

Abstract A diverse set of small RNAs is involved in the regulation of genome organization and gene expression in plants. These regulatory sRNAs play a central role for RNA in evolution and ontogeny in complex organisms, including forest tree species, providers of indispensable ecosystem services. RNA interference is a process that inhibits gene expression by double-stranded RNA and thus causes the degradation of target messenger RNA molecules. Targeted gene silencing by RNAi has been utilized in various crop plants in order to enhance their characteristics. For forest tree species, most of the successful RNAi modification has been conducted in poplar. Over the past 20 years, successful RNAi-mediated suppression of gene expression has been achieved with a variety of economically important traits. Moreover, the stability of RNAi-mediated transgene suppression has been confirmed in field-grown poplars. In this chapter, we describe examples of successful RNAi applications mainly in poplar but also provide some information about application of RNAi in pest control in forest tree species. Advantages and disadvantages of this technology with respect to the particular features of forest tree species will be discussed.


Author(s):  
Matthias Fladung ◽  
Hely Häggman ◽  
Suvi Sutela

Abstract A diverse set of small RNAs is involved in the regulation of genome organization and gene expression in plants. These regulatory sRNAs play a central role for RNA in evolution and ontogeny in complex organisms, including forest tree species, providers of indispensable ecosystem services. RNA interference is a process that inhibits gene expression by double-stranded RNA and thus causes the degradation of target messenger RNA molecules. Targeted gene silencing by RNAi has been utilized in various crop plants in order to enhance their characteristics. For forest tree species, most of the successful RNAi modification has been conducted in poplar. Over the past 20 years, successful RNAi-mediated suppression of gene expression has been achieved with a variety of economically important traits. Moreover, the stability of RNAi-mediated transgene suppression has been confirmed in field-grown poplars. In this chapter, we describe examples of successful RNAi applications mainly in poplar but also provide some information about application of RNAi in pest control in forest tree species. Advantages and disadvantages of this technology with respect to the particular features of forest tree species will be discussed.


1993 ◽  
Vol 268 (36) ◽  
pp. 27127-27132
Author(s):  
S Altuvia ◽  
W D Stein ◽  
S Goldenberg ◽  
S E Kane ◽  
I Pastan ◽  
...  

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Zhihao Fang ◽  
Yiqiu Hu ◽  
Jinhui Hu ◽  
Yanqin Huang ◽  
Shu Zheng ◽  
...  

AbstractAs the predominant modification in RNA, N6-methyladenosine (m6A) has attracted increasing attention in the past few years since it plays vital roles in many biological processes. This chemical modification is dynamic, reversible and regulated by several methyltransferases, demethylases and proteins that recognize m6A modification. M6A modification exists in messenger RNA and affects their splicing, nuclear export, stability, decay, and translation, thereby modulating gene expression. Besides, the existence of m6A in noncoding RNAs (ncRNAs) could also directly or indirectly regulated gene expression. Colorectal cancer (CRC) is a common cancer around the world and of high mortality. Increasing evidence have shown that the changes of m6A level and the dysregulation of m6A regulatory proteins have been implicated in CRC carcinogenesis and progression. However, the underlying regulation laws of m6A modification to CRC remain elusive and better understanding of these mechanisms will benefit the diagnosis and therapy. In the present review, the latest studies about the dysregulation of m6A and its regulators in CRC have been summarized. We will focus on the crucial roles of m6A modification in the carcinogenesis and development of CRC. Moreover, we will also discuss the potential applications of m6A modification in CRC diagnosis and therapeutics.


2009 ◽  
Vol 2009 ◽  
pp. 1-7 ◽  
Author(s):  
Constance Schmelzer ◽  
Mitsuaki Kitano ◽  
Gerald Rimbach ◽  
Petra Niklowitz ◽  
Thomas Menke ◽  
...  

MicroRNAs (miRs) are involved in key biological processes via suppression of gene expression at posttranscriptional levels. According to their superior functions, subtle modulation of miR expression by certain compounds or nutrients is desirable under particular conditions. Bacterial lipopolysaccharide (LPS) induces a reactive oxygen species-/NF-κB-dependent pathway which increases the expression of the anti-inflammatory miR-146a. We hypothesized that this induction could be modulated by the antioxidant ubiquinol-10. Preincubation of human monocytic THP-1 cells with ubiquinol-10 reduced the LPS-induced expression level of miR-146a to 78.9±13.22%. In liver samples of mice injected with LPS, supplementation with ubiquinol-10 leads to a reduction of LPS-induced miR-146a expression to 78.12±21.25%. From these consistent in vitro and in vivo data, we conclude that ubiquinol-10 may fine-tune the inflammatory response via moderate reduction of miR-146a expression.


2012 ◽  
Vol 198 (4) ◽  
pp. 529-544 ◽  
Author(s):  
Virginia Castilla-Llorente ◽  
Lee Spraggon ◽  
Miwako Okamura ◽  
Saif Naseeruddin ◽  
Matthew Adamow ◽  
...  

The microRNA (miRNA)-induced silencing complex (miRISC) controls gene expression by a posttranscriptional mechanism involving translational repression and/or promoting messenger RNA (mRNA) deadenylation and degradation. The GW182/TNRC6 (GW) family proteins are core components of the miRISC and are essential for miRNA function. We show that mammalian GW proteins have distinctive functions in the miRNA pathway, with GW220/TNGW1 being essential for the formation of GW/P bodies containing the miRISC. miRISC aggregation and formation of GW/P bodies sequestered and stabilized translationally repressed target mRNA. Depletion of GW220 led to the loss of GW/P bodies and destabilization of miRNA-targeted mRNA. These findings support a model in which the cellular localization of the miRISC regulates the fate of the target mRNA.


2010 ◽  
Vol 20 (1) ◽  
pp. 1-6 ◽  
Author(s):  
Sigurd Bøe ◽  
Stein Sæbøe-Larssen ◽  
Eivind Hovig

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