Search results for "codon"
showing 10 items of 196 documents
Designer membraneless organelles enable codon reassignment of selected mRNAs in eukaryotes.
2019
How to make an organelle in eukaryotes A key step in the evolution of complex organisms like eukaryotes was the organization of specific tasks into organelles. Reinkemeier et al. designed an artificial, membraneless organelle into mammalian cells to perform orthogonal translation. In response to a specific codon in a selected messenger RNA, ribosomes confined to this organelle were able to introduce chemical functionalities site-specifically, expanding the canonical set of amino acids. This approach opens possibilities in synthetic cell engineering and biomedical research. Science , this issue p. eaaw2644
Inducible Genetic Code Expansion in Eukaryotes
2020
Abstract Genetic code expansion (GCE) is a versatile tool to site‐specifically incorporate a noncanonical amino acid (ncAA) into a protein, for example, to perform fluorescent labeling inside living cells. To this end, an orthogonal aminoacyl‐tRNA‐synthetase/tRNA (RS/tRNA) pair is used to insert the ncAA in response to an amber stop codon in the protein of interest. One of the drawbacks of this system is that, in order to achieve maximum efficiency, high levels of the orthogonal tRNA are required, and this could interfere with host cell functionality. To minimize the adverse effects on the host, we have developed an inducible GCE system that enables us to switch on tRNA or RS expression whe…
Enhancement of premature stop codon readthrough in the CFTR gene by Ataluren (PTC124) derivatives.
2015
Abstract Premature stop codons are the result of nonsense mutations occurring within the coding sequence of a gene. These mutations lead to the synthesis of a truncated protein and are responsible for several genetic diseases. A potential pharmacological approach to treat these diseases is to promote the translational readthrough of premature stop codons by small molecules aiming to restore the full-length protein. The compound PTC124 (Ataluren) was reported to promote the readthrough of the premature UGA stop codon, although its activity was questioned. The potential interaction of PTC124 with mutated mRNA was recently suggested by molecular dynamics (MD) studies highlighting the importanc…
ENO1 gene product binds to the c-myc promoter and acts as a transcriptional repressor: relationship with Myc promoter-binding protein 1 (MBP-1).
2000
The Myc promoter-binding protein-1 (MBP-1) is a 37-38 kDa protein that binds to the c-myc P2 promoter and negatively regulates transcription of the protooncogene. MBP-1 cDNA shares 97% similarity with the cDNA encoding the glycolytic enzyme alpha-enolase and both genes have been mapped to the same region of human chromosome 1, suggesting the hypothesis that the two proteins might be encoded by the same gene. We show here data indicating that a 37 kDa protein is alternatively translated from the full-length alpha-enolase mRNA. This shorter form of alpha-enolase is able to bind the MBP-1 consensus sequence and to downregulate expression of a luciferase reporter gene under the control of the c…
Comparative Molecular Evolution of Primary (Buchnera) and Secondary Symbionts of Aphids Based on Two Protein-Coding Genes
2001
A+T content, phylogenetic relationships, codon usage, evolutionary rates, and ratio of synonymous versus non-synonymous substitutions have been studied in partial sequences of the atpD and aroQ/pheA genes of primary ( Buchnera) and secondary symbionts of aphids and a set of selected non-symbiotic bacteria, belonging to the five subdivisions of the Proteobacteria. Compared to the homologous genes of the last group, both genes belonging to Buchnera behave in a similar way, showing a higher A+T content, forming a monophyletic group, a loss in codon bias, especially in third base position, an evolutionary acceleration and an increase in the number of non-synonymous substitutions, confirming pre…
Cloning and sequencing of the dnaK region of Streptomyces coelicolor A3(2)
1993
Abstract The dnaK homologue of Streptomyces coelicolor A3(2) strain M145 has been cloned and sequenced. Nucleotide sequence analysis of a 2.5-kb region revealed an open reading frame (ORF) encoding a predicted DnaK protein of 618 amino acids (Mr = 66 274). The dnaK coding sequence displays extreme codon bias and shows a strong preference for CGY and GGY, for Arg and Gly codons, respectively. The predicted DnaK sequence has a high Lys:Arg ratio which is not typical of streptomycete proteins. The region immediately downstream from dnaK contains an ORF for a GrpE-like protein; the predicted start codon of grpE overlaps the last two codons of dnaK, indicating that the two genes are translationa…
A frame shift mutation in a hot spot region of the nuclear autoantigen La (SS-B).
1996
A hot spot region was identified in the exon 7 of the nuclear autoantigen La (SS-B). Two La cDNAs were identified which contained a frame shift mutation in the hot spot region. One La cDNA was isolated from a cDNA library made from peripheral blood lymphocytes of an autoimmune patient with primary Sjogren's Syndrome, the other La cDNA was isolated from a human liver cDNA library. The patient's La cDNA had a deletion and the liver La cDNA had an insert of an (A)-residue at the same position. Inserts of 4, 16 and 24 more or less homogeneous (A)-residues were found at the same site in the three La retropseudogenes. The hot spot region located in one of the major autoepitope regions of the La a…
The human p53 gene mutated at position 249per se is not sufficient to immortalize human liver cells
1999
A particular point mutation of the tumor suppressor gene p53, namely a G→T transversion at the third base of codon 249, is frequently detected in primary hepatocellular carcinomas from patients living in areas where the levels of dietary exposure to aflatoxin B 1 and the rates of infection with the hepatitis B virus are very high. Very recently, a nontumorigenic liver epithelial cell line (HACL-1) with a finite life-span and expressing a number of hepatocyte-specific markers was established from a human hepatocellular adenoma in our laboratory. To analyze the role of mutated p53 in the immortalization of human liver cells, we transfected HACL-1 cells with an expression vector containing a h…
Toward a Rationale for the PTC124 (Ataluren) Promoted Readthrough of Premature Stop Codons: A Computational Approach and GFP-Reporter Cell-Based Assay
2014
The presence in the mRNA of premature stop codons (PTCs) results in protein truncation responsible for several inherited (genetic) diseases. A well-known example of these diseases is cystic fibrosis (CF), where approximately 10% (worldwide) of patients have nonsense mutations in the CF transmembrane regulator (CFTR) gene. PTC124 (3-(5-(2-fluorophenyl)-1,2,4-oxadiazol-3-yl)-benzoic acid), also known as Ataluren, is a small molecule that has been suggested to allow PTC readthrough even though its target has yet to be identified. In the lack of a general consensus about its mechanism of action, we experimentally tested the ability of PTC124 to promote the readthrough of premature termination c…
Taxonomic investigation on Allium hirtovaginum group (Amaryllidaceae) from East Mediterranean area
2021
Within taxonomic studies on Allium sect. Codonoprasum from Mediterranean flora, populations belonging to A. hirtovaginum Candargy group were examined. Based on field investigation and herbarium surveyes, this group is represented by very critical and not well known taxa, distributed in the East Mediterranean, showing a marked morphological variability. Currently, the species referable to this group in addition to A. hirtovaginum are also A. pilosum Sibth. & Sm., A. aeginiense Brullo, Giusso & Terrasi and A. nerimaniae Koçyiğit & Kaya. Besides, other 13 species are here described as new to science, they are A. pythagoricum, A. pignattii, A. hippocraticum, A. abanticum, A. velutin…