Elmar Wahle
Prof. Elmar Wahle
Institute of Biochemistry and Biotechnology/General Biochemistry
Kurt-Mothes-Straße 3
06120 Halle (Saale)
phone: +49 (0) 345-55 24920
elmar.wahle@biochemtech.uni-halle.de
The CCR4-NOT complex of Drosophila melanogaster
Gene expression is regulated not only at the level of transcription, but also at all subsequent steps, including translation and mRNA decay. Deadenylation , i. e. removal of the poly(A) tail by 3'-exonucleases, is normally the first and rate-limiting step of mRNA degradation. Degradation of mRNA is an important regulatory process: Decay rates vary widely between different mRNAs, can be regulated in a specific manner and determine, together with the rate of transcription, the steady-state levels of mRNAs and, thus, the translational output. The CCR4-NOT complex is the main deadenylase in all cells and organisms investigated so far. Deadenylation no only promotes the subsequent steps of mRNA decay but also inhibits translation. However, evidence has recently been published that the CCR4-NOT complex inhibits translation not only by catalyzing poly(A) tail removal, but also directly, through unknown mechanisms.
We investigate the function of the CCR4-NOT complex in Drosophila melanogaster. Our focus is on the composition and function of the complex itself and on its role in controlling the hsp70 mRNA and the nanos mRNA.
The CCR4-NOT complex consists of more than half a dozen subunits, two of which function as 3' exonucleases. We are attempting to reconstitute the entire complex by baculovirus-mediated expression.
The nanos-mRNA is a maternal mRNA playing a central role in early embryo development. The regulation of its localization, translation and stability is essential for the establishment of a concentration gradient of the nanos protein in the embryo, which in turn serves to establish the anterior-posterior axis. Both the translational repression and the rapid deadenylation of the nanos-mRNA can be observed in a cell-free system from early embryos. The CCR4-NOT complex is known to catalyze the deadenylation and is likely to be involved in the translation control as well. One important aim of our project is a molecular understanding of the mechanisms in deadenylation and translation repression.
Funds from the research program are used to support Dr. Claudia Temme, who also participates in running the running the program as a scientific coordinator.