Functional expression of ribozymes in Apicomplexa: Towards exogenous control of gene expression by inducible RNA-cleavage

Agop-Nersesian, C., Pfahler, J., Lanzer, M. and Meissner, M. (2008) Functional expression of ribozymes in Apicomplexa: Towards exogenous control of gene expression by inducible RNA-cleavage. International Journal for Parasitology, 38(6), pp. 673-681. (doi: 10.1016/j.ijpara.2007.10.015)

Abstract

The ability to control expression of a specific gene is a prerequisite to understand the function of essential genes. Many gene regulation systems operate on the transcriptional level by employing heterologous cis- and trans-acting elements. Recently, novel approaches employing autocatalytic RNA have been reported for different organisms. Here we show specific downregulation of gene expression in the apicomplexan parasites Toxoplasma gondii and Plasmodium falciparum, employing self-cleaving ribozymes integrated into the transcriptional unit of different genes. Moreover, we demonstrate the potential to specifically upregulate reporter gene expression by employment of the recently identified ribozyme inhibitor toyocamycin. At the RNA-level, we were able to significantly stabilise the mRNA in T gondii. Furthermore we show that the adenosine analogue toyocamycin needs to be phosphorylated by adenosine kinase in order to act as an inhibitor for hammerhead ribozymes, since neither upregulation of reporter gene expression nor a toxic effect of toyocamycin can be detected in parasites that do not express the enzyme adenosine kinase.

• Item Type: Articles
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Meissner, Professor Markus
• Authors: Agop-Nersesian, C., Pfahler, J., Lanzer, M., and Meissner, M.
• Subjects: Q Science > QH Natural history > QH426 Genetics
• College/School: College of Medical Veterinary and Life Sciences > School of Infection & Immunity
• Journal Name: International Journal for Parasitology
• ISSN: 0020-7519
• ISSN (Online): 1879-0135
• Published Online: 06 November 2007