Project Details
Projekt
RNA-mediated regulation of transcription during herpes simplex virus 1 infection
Applicant
Professor Dr. Markus Landthaler
Subject Area
Virology
Term
since 2021
Project identifier
Deutsche Forschungsgemeinschaft (DFG) - Project number 443644894
Herpes simplex virus (HSV-1) is a double-stranded DNA virus replicating in the nucleus, and depends on a plethora of host cell factors for transcription and processing of its mRNAs. RNA-binding proteins (RBPs) and non-coding RNAs, such as enhancer RNAs (eRNAs) and long non-coding RNAs (lncRNAs) modulate these processes on several levels. This spans processes from recruiting of transcription factors to promoters, chromatin remodeling, facilitating RNA polymerase II to modulating promoter-proximal pausing and pause release. In this project, we investigate how RNA-protein interactions fine-tune transcriptional output in HSV-1 infection. Interestingly, we discovered that the viral transcription factor ICP4 crosslinks to RNA. To directly examine the function of host RBPs, we engineered HCT116 auxin-degron cells for rapid depletion of a number of proteins with RNA-binding activity that are involved in promoter proximal pausing, its release and transcriptional elongation as well as nuclear RBPs identified previously to influence HSV-1 infection. Based on our preliminary data, this collaborative project aims to systematically examine the molecular RNA-based mechanisms of HSV-1 transcription. The project has three primary objectives: (i) identify ICP4 domain functions and investigate the relevance of RNA interactions in early viral transcription, (ii) functional analysis of RBPs involved in transcriptional initiation and elongation, and (iii) examine the role of enhancer RNAs in the regulation of the transcriptional program in HSV-1 infected cells. In summary, this project promises to significantly advance our understanding of early HSV-1 transcriptional events and provides the potential for applying antisense oligonucleotide to sequence-specifically interfere with RNA function as a novel therapeutic approach.
DFG Programme
Research Units
