Programmed ribosomal frameshifting is used by many viruses to regulate the production of structural and enzymatic proteins. Altering the frameshifting efficiencies disrupts the virus life cycle and eliminates or reduces virus production. Ribosomal frameshifting therefore provides a unique target on which antiviral agents can function. This article describes a series of rapid assay strategies that have been developed and used to identify potential antiviral agents that target programmed -1 ribosomal frameshifting.
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http://dx.doi.org/10.1016/s0167-7799(97)01167-0 | DOI Listing |
Nucleic Acids Res
January 2025
Department of Chemical Engineering, Pohang University of Science and Technology (POSTECH), Pohang 37673, Republic of Korea.
Biological resources, such as sequence information, genetic traits, materials and strains, pose risks when inadvertently released or deliberately misused. To address these concerns, we developed Quadruplet COdon DEcoding (QCODE), a versatile genetic biocontainment strategy that introduces a quadruplet codon (Q-codon) causing frameshifts, hindering proper gene expression. Strategically incorporating Q-codons in multiple genes prevents genetic trait escape, unallowed proliferation of microbial strains and unauthorized leakages of genetic materials.
View Article and Find Full Text PDFImmunity
December 2024
Division of Oncogenomics, Oncode institute, the Netherlands Cancer Institute, Amsterdam, the Netherlands; Erasmus MC, Department of Genetics, Rotterdam University, Rotterdam, the Netherlands. Electronic address:
Prolonged exposure to interferon-gamma (IFNγ) and the associated increased expression of the enzyme indoleamine 2,3-dioxygenase 1 (IDO1) create an intracellular shortage of tryptophan in the cancer cells, which stimulates ribosomal frameshifting and tryptophan to phenylalanine (W>F) codon reassignments during protein synthesis. Here, we investigated whether such neoepitopes can be useful targets of adoptive T cell therapy. Immunopeptidomic analyses uncovered hundreds of W>F neoepitopes mainly presented by the HLA-A24:02 allele.
View Article and Find Full Text PDFNucleic Acids Res
December 2024
Innovative Genomics Institute, University of California, Berkeley, Berkeley, CA 94720, USA.
West Nile virus (WNV) requires programmed -1 ribosomal frameshifting for translation of the viral genome. The efficiency of WNV frameshifting is among the highest known. However, it remains unclear why WNV exhibits such a high frameshifting efficiency.
View Article and Find Full Text PDFNew Phytol
December 2024
College of Life Science, Henan Agricultural University, Zhengzhou, 450002, China.
Protein isoforms (PIs) play pivotal roles in regulating plant growth and development that confer adaptability to diverse environmental conditions. PIs are widely present in plants and generated through alternative splicing (AS), alternative polyadenylation (APA), alternative initiation (AI), and ribosomal frameshifting (RF) events. The widespread presence of PIs not only significantly increases the complexity of genomic information but also greatly enriches regulatory networks and enhances their flexibility.
View Article and Find Full Text PDFNucleic Acids Res
December 2024
Division of Oncogenomics, Oncode Institute, The Netherlands Cancer Institute, Plesmanlaan 121, 1066CX, Amsterdam, the Netherlands.
Messenger RNA (mRNA) translation is a tightly controlled process frequently deregulated in cancer. Key to this deregulation are transfer RNAs (tRNAs), whose expression, processing and post-transcriptional modifications are often altered in cancer to support cellular transformation. In conditions of limiting levels of amino acids, this deregulated control of protein synthesis leads to aberrant protein production in the form of ribosomal frameshifting or misincorporation of non-cognate amino acids.
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