Engineered riboswitches control gene expression by small molecules

2005 ◽  
Vol 33 (3) ◽  
pp. 474-476 ◽  
Author(s):  
B. Suess

We have developed conditional gene expression systems based on engineered small-molecule-binding riboswitches. Tetracycline-dependent regulation can be imposed on an mRNA in yeast by inserting an aptamer in its 5′-untranslated region. Biochemical and genetic analyses determined that binding of the ligand tetracycline leads to a pseudoknot-like linkage within the aptamer structure, thereby inhibiting the initial steps of translation. A second translational control element was designed by combining a theophylline aptamer with a communication module for which a 1 nt slipping mechanism had been proposed. This structural element was inserted close to the bacterial ribosomal binding site at a position just interfering with translation in the non-ligand-bound form. Addition of the ligand then shifts the inhibitory element to a distance that permits efficient translation.

Development ◽  
2002 ◽  
Vol 129 (14) ◽  
pp. 3325-3334 ◽  
Author(s):  
Ira E. Clark ◽  
Krista C. Dobi ◽  
Heather K. Duchow ◽  
Anna N. Vlasak ◽  
Elizabeth R. Gavis

Translational repression of maternal nanos (nos) mRNA by a cis-acting Translational Control Element (TCE) in the nos 3′UTR is critical for anterior-posterior patterning of the Drosophila embryo. We show, through ectopic expression experiments, that the nos TCE is capable of repressing gene expression at later stages of development in neuronal cells that regulate the molting cycle. Our results predict additional targets of TCE-mediated repression within the nervous system. They also suggest that mechanisms that regulate maternal mRNAs, like TCE-mediated repression, may function more widely during development to spatially or temporally control gene expression.


2005 ◽  
Vol 2005 (Fall) ◽  
Author(s):  
Beatrix Suess ◽  
Shane Hanson ◽  
Michael Müller

2020 ◽  
Vol 48 (4) ◽  
pp. 1645-1659
Author(s):  
Denis Hartmann ◽  
Jefferson M. Smith ◽  
Giacomo Mazzotti ◽  
Razia Chowdhry ◽  
Michael J. Booth

The expression of a gene to a protein is one of the most vital biological processes. The use of light to control biology offers unparalleled spatiotemporal resolution from an external, orthogonal signal. A variety of methods have been developed that use light to control the steps of transcription and translation of specific genes into proteins, for cell-free to in vivo biotechnology applications. These methods employ techniques ranging from the modification of small molecules, nucleic acids and proteins with photocages, to the engineering of proteins involved in gene expression using naturally light-sensitive proteins. Although the majority of currently available technologies employ ultraviolet light, there has been a recent increase in the use of functionalities that work at longer wavelengths of light, to minimise cellular damage and increase tissue penetration. Here, we discuss the different chemical and biological methods employed to control gene expression, while also highlighting the central themes and the most exciting applications within this diverse field.


Author(s):  
C. Boulard ◽  
J. Thévenin ◽  
O. Tranquet ◽  
V. Laporte ◽  
L. Lepiniec ◽  
...  

1974 ◽  
Vol 71 (12) ◽  
pp. 5057-5061 ◽  
Author(s):  
T. Barrett ◽  
D. Maryanka ◽  
P. H. Hamlyn ◽  
H. J. Gould

2012 ◽  
Vol 2012 ◽  
pp. 1-10 ◽  
Author(s):  
Godfrey Grech ◽  
Marieke von Lindern

Organisation of RNAs into functional subgroups that are translated in response to extrinsic and intrinsic factors underlines a relatively unexplored gene expression modulation that drives cell fate in the same manner as regulation of the transcriptome by transcription factors. Recent studies on the molecular mechanisms of inflammatory responses and haematological disorders indicate clearly that the regulation of mRNA translation at the level of translation initiation, mRNA stability, and protein isoform synthesis is implicated in the tight regulation of gene expression. This paper outlines how these posttranscriptional control mechanisms, including control at the level of translation initiation factors and the role of RNA binding proteins, affect hematopoiesis. The clinical relevance of these mechanisms in haematological disorders indicates clearly the potential therapeutic implications and the need of molecular tools that allow measurement at the level of translational control. Although the importance of miRNAs in translation control is well recognised and studied extensively, this paper will exclude detailed account of this level of control.


2021 ◽  
Vol 120 (3) ◽  
pp. 354a
Author(s):  
Anand P. Singh ◽  
Ping Wu ◽  
Eric F. Wieschaus ◽  
Jared E. Toettcher ◽  
Thomas Gregor

Development ◽  
1999 ◽  
Vol 126 (4) ◽  
pp. 659-669 ◽  
Author(s):  
S.E. Bergsten ◽  
E.R. Gavis

Patterning of the anterior-posterior body axis during Drosophila development depends on the restriction of Nanos protein to the posterior of the early embryo. Synthesis of Nanos occurs only when maternally provided nanos RNA is localized to the posterior pole by a large, cis-acting signal in the nanos 3′ untranslated region (3′UTR); translation of unlocalized nanos RNA is repressed by a 90 nucleotide Translational Control Element (TCE), also in the 3′UTR. We now show quantitatively that the majority of nanos RNA in the embryo is not localized to the posterior pole but is distributed throughout the cytoplasm, indicating that translational repression is the primary mechanism for restricting production of Nanos protein to the posterior. Through an analysis of transgenes bearing multiple copies of nanos 3′UTR regulatory sequences, we provide evidence that localization of nanos RNA by components of the posteriorly localized germ plasm activates its translation by preventing interaction of nanos RNA with translational repressors. This mutually exclusive relationship between translational repression and RNA localization is mediated by a 180 nucleotide region of the nanos localization signal, containing the TCE. These studies suggest that the ability of RNA localization to direct wild-type body patterning also requires recognition of multiple, unique elements within the nanos localization signal by novel factors. Finally, we propose that differences in the efficiencies with which different RNAs are localized result from the use of temporally distinct localization pathways during oogenesis.


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