Synchronicity: policing multiple aspects of gene expression by Ctk1
- Michael Hampsey1 and
- Terri Goss Kinzy2,3
- 1 Department of Biochemistry, Division of Nucleic Acid Enzymology, University of Medicine and Dentistry of New Jersey-Robert Wood Johnson Medical School, Piscataway, New Jersey 08854, USA;
- 2 Department of Molecular Genetics, Microbiology and Immunology, University of Medicine and Dentistry of New Jersey-Robert Wood Johnson Medical School, Piscataway, New Jersey 08854, USA
This extract was created in the absence of an abstract.
Transcription and translation are coordinated events in all organisms. In prokaryotes, the process that couples these two events is clear: The ribosome begins translation of the nascent mRNA while the DNA template is still being transcribed. Indeed, cotranscriptional protein synthesis underlies key regulatory mechanisms in bacteria, including attenuation, the mechanism that regulates RNA polymerase processivity in response to ribosome movement along the mRNA. But how is transcription coordinated with translation in eukaryotic organisms, where mRNA is synthesized in the nucleus and protein synthesis occurs in the cytoplasm? Although these two events are spatially distinct, separated by the nuclear envelope, efficient control of gene expression necessarily requires that transcription and translation be regulated in a coordinated manner. As an example, dFOXO-mediated transcriptional activation produces both an inhibitor of cap-dependent translation, eukaryotic translation initiation factor 4E (eIF4E)-BP, and a form of the insulin receptor mRNA that is translated by a cap-independent mechanism (Marr et al. 2007). In addition, translation requires a fully and accurately processed mRNA, and has mechanisms to help sense that appropriate processing has occurred.
In the absence of physical coupling of transcription and translation, how are these two processes coordinated in eukaryotes? In this issue of Genes & Development, Röther and Sträßer (2007) report that the Ctk1 kinase, a key enzyme that facilitates passage of RNA polymerase II (Pol II) through specific stages of the transcription cycle, is also found in the cytoplasm associated with ribosomes actively engaged in protein synthesis (Fig. 1). Their work defines a physiological role for Ctk1 in translation by showing that cellular depletion of Ctk1 decreases total protein synthesis as well as the fidelity of translation elongation. These effects are likely to be a direct effect of Ctk1, since they identified the small ribosomal subunit protein rpS2 as the specific target of the …
