Stimulation of ribosomal frameshifting by antisense LNA

Chien Hung Yu, Mathieu H.M. Noteborn, René C.L. Olsthoorn

Research output: Contribution to journalArticle

22 Citations (Scopus)

Abstract

Programmed ribosomal frameshifting is a translational recoding mechanism commonly used by RNA viruses to express two or more proteins from a single mRNA at a fixed ratio. An essential element in this process is the presence of an RNA secondary structure, such as a pseudoknot or a hairpin, located downstream of the slippery sequence. Here, we have tested the efficiency of RNA oligonucleotides annealing downstream of the slippery sequence to induce frameshifting in vitro. Maximal frameshifting was observed with oligonucleotides of 12-18nt. Antisense oligonucleotides bearing locked nucleid acid (LNA) modifications also proved to be efficient frameshift-stimulators in contrast to DNA oligonucleotides. The number, sequence and location of LNA bases in an otherwise DNA oligonucleotide have to be carefully manipulated to obtain optimal levels of frameshifting. Our data favor a model in which RNA stability at the entrance of the ribosomal tunnel is the major determinant of stimulating slippage rather than a specific three-dimensional structure of the stimulating RNA element.

Original languageEnglish
Pages (from-to)8277-8283
Number of pages7
JournalNucleic acids research
Volume38
Issue number22
DOIs
Publication statusPublished - 2010 Dec

All Science Journal Classification (ASJC) codes

  • Genetics

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