scholarly journals Therapeutic promise of engineered nonsense suppressor tRNAs

2021 ◽  
Author(s):  
Joseph J. Porter ◽  
Christina S. Heil ◽  
John D. Lueck
Keyword(s):  
Nonsense Suppressor

scholarly journals Identification of the Genes Encoding the Cytosolic Translation Release Factors from Podospora anserina and Analysis of Their Role During the Life Cycle

Genetics ◽  
1998 ◽  
Vol 149 (4) ◽  
pp. 1763-1775 ◽  
Author(s):  
Bénédicte Gagny ◽  
Philippe Silar
Keyword(s):  
Life Span ◽  
Translation Termination ◽  
Podospora Anserina ◽  
Terminal Region ◽  
Terminal Portion ◽  
Nonsense Mutations ◽  
Translation Fidelity ◽  
Reproductive Impairment ◽  
Genes Encoding ◽  
Nonsense Suppressor

Abstract In an attempt to decipher their role in the life history and senescence process of the filamentous fungus Podospora anserina, we have cloned the su1 and su2 genes, previously identified as implicated in cytosolic translation fidelity. We show that these genes are the equivalents of the SUP35 and SUP45 genes of Saccharomyces cerevisiae, which encode the cytosolic translation termination factors eRF3 and eRF1, respectively. Mutations in these genes that suppress nonsense mutations may lead to drastic mycelium morphology changes and sexual impairment but have little effect on life span. Deletion of su1, coding for the P. anserina eRF3, is lethal. Diminution of its expression leads to a nonsense suppressor phenotype whereas its overexpression leads to an antisuppressor phenotype. P. anserina eRF3 presents an N-terminal region structurally related to the yeast eRF3 one. Deletion of the N-terminal region of P. anserina eRF3 does not cause any vegetative alteration; especially life span is not changed. However, it promotes a reproductive impairment. Contrary to what happens in S. cerevisiae, deletion of the N terminus of the protein promotes a nonsense suppressor phenotype. Genetic analysis suggests that this domain of eRF3 acts in P. anserina as a cis-activator of the C-terminal portion and is required for proper reproduction.

Inactivation of nonsense suppressor transfer RNA genes in Schizosaccharomyces pombe

1986 ◽  
Vol 188 (3) ◽  
pp. 343-353 ◽  
Author(s):  
Wolf-Dietrich Heyer ◽  
Peter Münz ◽  
Hanspeter Amstutz ◽  
Riccardo Aebi ◽  
Cristoph Gysler ◽  
...  
Keyword(s):  
Schizosaccharomyces Pombe ◽  
Transfer Rna ◽  
Nonsense Suppressor ◽  
Rna Genes

Recessive Lethal Nonsense Suppressor in Escherichia coli which inserts Glutamine

Nature ◽  
1969 ◽  
Vol 223 (5213) ◽  
pp. 1340-1342 ◽  
Author(s):  
LARRY SOLL ◽  
PAUL BERG
Keyword(s):  
Escherichia Coli ◽  
Recessive Lethal ◽  
Nonsense Suppressor

scholarly journals Nonsense suppressor therapies rescue peroxisome lipid metabolism and assembly in cells from patients with specific PEX gene mutations

2011 ◽  
Vol 112 (5) ◽  
pp. 1250-1258 ◽  
Author(s):  
Patricia K. Dranchak ◽  
Erminia Di Pietro ◽  
Ann Snowden ◽  
Nathan Oesch ◽  
Nancy E. Braverman ◽  
...  
Keyword(s):  
Lipid Metabolism ◽  
Gene Mutations ◽  
Nonsense Suppressor ◽  
In Cells

scholarly journals LAC4 IS THE STRUCTURAL GENE FOR β-GALACTOSIDASE IN KLUYVEROMYCES LACTIS

Genetics ◽  
1981 ◽  
Vol 98 (4) ◽  
pp. 729-745
Author(s):  
R Michael Sheetz ◽  
Robert C Dickson
Keyword(s):  
Thermal Stability ◽  
Structural Gene ◽  
Gel Electrophoresis ◽  
Kluyveromyces Lactis ◽  
Two Dimensional ◽  
Galactosidase Activity ◽  
Wild Type ◽  
Nonsense Suppressor ◽  
Hydrolysis Of ◽  
Thermal Stability Of

ABSTRACT Using genetic and biochemical techniques, we have determined that β-galactosidase in the yeast Kluyveromyces lactis is coded by the LAC4 locus. The following data support this conclusion: (1) mutations in this locus result in levels of β-galactosidase activity 100-fold lower than levels in uninduced wild type and all other lac- mutants; (2) three of five lac4 mutations are suppressible by an unlinked suppressor whose phenotype suggests that it codes for a nonsense suppressor tRNA; (3) a Lac+ revertant, bearing lac4–14 and this unlinked suppressor, has subnormal levels of β-galactosidase activity, and the Km for hydrolysis of o-nitrophenyl-β, D-galactoside and the thermal stability of the enzyme are altered; (4) the level of β-galactosidase activity per cell is directly proportional to the number of copies of LAC4; (5) analysis of cell-free extracts of strains bearing mutations in LAC4 by two-dimensional acryl-amide gel electrophoresis shows that strains bearing lac4–23 and lac4–30 contain an inactive β-galactosidase whose subunit co-electrophoreses with the wild-type subunit, while no subunit or fragment of the subunit is obs0ervable in lac4–8, lac4–14 or lac4–29 mutants; (6) of all lac4 mutants, only those bearing lac4–23 or lac4–30 contain a protein that cross-reacts with anti-β-galactosidase antibody, a finding consistent with the previous result; and (7) β-galactosidase activity in several Lac+ revertants of strains carrying lac4–23 or lac4–30 has greatly decreased thermostability.

scholarly journals Yeast Sup35 Prion Structure: Two Types, Four Parts, Many Variants

2019 ◽  
Vol 20 (11) ◽  
pp. 2633 ◽  
Author(s):  
Alexander Dergalev ◽  
Alexander Alexandrov ◽  
Roman Ivannikov ◽  
Michael Ter-Avanesyan ◽  
Vitaly Kushnirov
Keyword(s):  
Amino Acid ◽  
Ex Vivo ◽  
Mass Spectrometric ◽  
Proteinase K ◽  
Amino Acid Residues ◽  
Structural Variants ◽  
Spectrometric Identification ◽  
Mass Spectrometric Identification ◽  
Nonsense Suppressor ◽  
Different Origin

The yeast [PSI+] prion, formed by the Sup35 (eRF3) protein, has multiple structural variants differing in the strength of nonsense suppressor phenotype. Structure of [PSI+] and its variation are characterized poorly. Here, we mapped Sup35 amyloid cores of 26 [PSI+] ex vivo prions of different origin using proteinase K digestion and mass spectrometric identification of resistant peptides. In all [PSI+] variants the Sup35 amino acid residues 2–32 were fully resistant and the region up to residue 72 was partially resistant. Proteinase K-resistant structures were also found within regions 73–124, 125–153, and 154–221, but their presence differed between [PSI+] isolates. Two distinct digestion patterns were observed for region 2–72, which always correlated with the “strong” and “weak” [PSI+] nonsense suppressor phenotypes. Also, all [PSI+] with a weak pattern were eliminated by multicopy HSP104 gene and were not toxic when combined with multicopy SUP35. [PSI+] with a strong pattern showed opposite properties, being resistant to multicopy HSP104 and lethal with multicopy SUP35. Thus, Sup35 prion cores can be composed of up to four elements. [PSI+] variants can be divided into two classes reliably distinguishable basing on structure of the first element and the described assays.

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