The long-term objectives of this proposal are to 1) understand the relationship between the capping enzyme processing factors and transcription elongation and initiation, and 2) determine the mechanism underlying the processing event of capping and response to cellular stress. Our lab has previously determined that the mapping enzymes methyltransferase (MT) and guanylyltransferase (GT) can bind the CTD domain of RNA pol II, and that MT can act as a transcription factor in yeast.
My first aim will explore the hypothesis that capping enzymes can function to enhance pol II regulated transcription in higher eukaryotes using CHIP and nuclear run-on analysis. The integration of transcription and processing is still poorly understood but is likely to be of significance for control of gene expression, and this proposal may help elucidate this relationship.
My second aim explores the hypothesis that capping enzyme recruitment to pol II is a regulated process during stress response. I have preliminary evidence that suggests an increase in uncapped heat shock transcripts after stress. Considering that recent reports correlating cap-independent translation with genes associated with stress response, a better understanding of this phenomenon could be of medical importance. ? ?
| Brannan, Kris; Kim, Hyunmin; Erickson, Benjamin et al. (2012) mRNA decapping factors and the exonuclease Xrn2 function in widespread premature termination of RNA polymerase II transcription. Mol Cell 46:311-24 |
| Glover-Cutter, Kira; Larochelle, Stéphane; Erickson, Benjamin et al. (2009) TFIIH-associated Cdk7 kinase functions in phosphorylation of C-terminal domain Ser7 residues, promoter-proximal pausing, and termination by RNA polymerase II. Mol Cell Biol 29:5455-64 |
| Glover-Cutter, Kira; Kim, Soojin; Espinosa, Joaquin et al. (2008) RNA polymerase II pauses and associates with pre-mRNA processing factors at both ends of genes. Nat Struct Mol Biol 15:71-8 |
