RNA processing and stability represent two post-transcriptional mechanisms by which gene expression may be regulated. With processing, sequences can be altered, targeting signals added, protein binding regions created, and functional activities changed. The importance of RNA processing is illustrated by beta-thalasemia in which an aberration produces a disease state. Similarly, modifications in RNA stability can have profound effects on gene expression. Some oncogene, growth factor, and cytokine mRNAs appear to contain signals which define their relatively short half-lives under normal conditions. However, their mRNA stability can apparently be altered, and it has been found to be prolonged in some cases in which increased gene expression would be expected. A prolongation of c-myc mRNA half-life has been noted in lymphoma, and the cytokine mRNAs have decreased degradation following T-cell stimulation. These examples suggest that mRNA processing and stability effect expression, but in general, they are poorly understood means of post-transcriptional gene regulation. A system in which post-transcriptional RNA modification and stability are known to be factors has been selected. Trypanosome mitochondria have unusual 3' end processing and regulation of their rRNAs. Investigations of the mechanisms by which these are achieved will permit further definition of the mechanisms involved in this form of post-transcriptional gene control. The research will focus on: l) delineation of the mechanism of 3' terminus formation by developing an in vitro system and defining the requirements for processing activity; 2) determination of the mechanism of variable rRNA stability and evaluation of any role 3' terminus formation may have in rRNA stability through degradation, gel shift mobility, and endonuclease protection studies. This work may improve our understanding of the process of post-transcriptional regulation of gene expression. Knowledge of such a fundamental process could give insight into the mechanisms involved in cell growth and differentiation.
| McManus, M T; Adler, B K; Pollard, V W et al. (2000) Trypanosoma brucei guide RNA poly(U) tail formation is stabilized by cognate mRNA. Mol Cell Biol 20:883-91 |
| Adler, B K; Hajduk, S L (1997) Guide RNA requirement for editing-site-specific endonucleolytic cleavage of preedited mRNA by mitochondrial ribonucleoprotein particles in Trypanosoma brucei. Mol Cell Biol 17:5377-85 |
| Adler, B K; Hajduk, S L (1994) Mechanisms and origins of RNA editing. Curr Opin Genet Dev 4:316-22 |
