Work

A novel therapeutic approach for genetic diseases by introduction of suppressor tRNA

Year: 2006

Type: conference-paper

Abstract: The appearance of the premature translation termination codons (PTCs) in the transcript is the major cause of human genetic diseases. PTC-containing transcripts are rapidly degraded through nonsense-mediated decay (NMD) pathway. If such mRNA transcripts were translated in frame like normal transcripts, it would afford not only restoration of the level of full-length protein but also prevention of mRNA degradation by the NMD pathway. Here we describe a novel approach to read through PTC-containing mRNAs using suppressor tRNA that is introduced to cells by transfection. Luciferase reporter gene assay showed that nonsense and four-base codons were suppressed by the corresponding suppressor tRNAs derived from human tRNA(Ser). We also demonstrated that transfection of the suppressor tRNA to Ullrich disease fibroblasts, possessing a frameshift mutation in the collagen VI alpha2 gene, induced the upregulation of the collagen VI alpha2 mRNA and accumulation of the collagen VI protein. PTC suppression potentially provides a novel therapeutic means to rescue various PTC-related diseases.

Source: Nucleic Acids Symposium Series

DOI: 10.1093/nass/nrl119

Authors: Yusuke Sako, Fusako Usuki, Hiroaki Suga

Institutions: Research Center for Advanced Science and Technology, The University of Tokyo, The University of Tokyo

Language: English

Topic: RNA and protein synthesis mechanisms

Subfield: Molecular Biology

Field: Biochemistry, Genetics and Molecular Biology

Domain: Life Sciences

SDG: Good health and well-being

Open Access status: bronze

OpenAlex ID: W2078223063