Regulation of cytoplasmic RNA stability: lessons from drosophila

The process of RNA degradation is a critical level of regulation contributing to the control of gene expression. In the last two decades a number of studies have shown the specific and targeted nature of RNA decay and its importance in maintaining homeostasis. The key players within the pathways of RNA decay are well conserved with their mutation or disruption resulting in distinct phenotypes as well as human disease. Model organisms including Drosophila melanogaster have played a substantial role in elucidating the mechanisms conferring control over RNA stability. A particular advantage of this model organism is that the functions of ribonucleases can be assessed in the context of natural cells within tissues in addition to individual immortalised cells in culture. Drosophila RNA stability research has demonstrated how the cytoplasmic decay machines, such as the exosome, Dis3L2 and Xrn1, are responsible for regulating specific processes including apoptosis, proliferation, wound healing and fertility. The work discussed here has begun to identify specific mRNA transcripts that appear sensitive to specific decay pathways representing mechanisms through which the ribonucleases control mRNA stability. Drosophila research has also contributed to our knowledge of how specific RNAs are targeted to the ribonucleases including AU rich elements, miRNA targeting and 3’ tailing. Increased understanding of these mechanisms is critical to elucidating the control elicited by the cytoplasmic ribonucleases which is relevant to human disease.