Nara Lee, PhD

Noncoding RNA-mediated regulation of transcription  

With the advent of deep sequencing technology, a plethora of noncoding RNAs (ncRNAs) with as yet unknown functions has been discovered. A subset of these ncRNAs is found in the nucleus and thus has been proposed to contribute to transcription regulation. How and which ncRNAs regulate transcription is the overarching question of the Lee lab. 

Epstein-Barr virus (EBV) is an oncogenic gamma-herpesvirus with a prevalence of over 90% in the human population. It is best known as the causative agent of mononucleosis, but is also associated with several types of cancers, such as lymphomas and carcinomas. EBV expresses two highly abundant nuclear ncRNAs called EBER1 (EBV-encoded RNA 1) and EBER2. The function of EBER1 is poorly understood, while EBER2 has recently been shown to facilitate the recruitment of an interacting transcription factor, PAX5, to the viral genome. Intriguingly, the recruitment mechanism entails RNA-RNA base pairing between EBER2 and nascent transcripts that originate from the target site. Upon recruitment, the EBER2-PAX5 ribonucleoprotein complex affects the transcription of nearby genes, probably by influencing the chromatin conformation of this region of the viral genome. 

Our lab is studying the RNA-RNA based recruitment mechanism utilized in EBV in greater detail with the goal to extrapolate our findings to the host cell. Since viruses often adopt existing mechanisms from their hosts, our observation suggests that cellular ncRNAs might exist that use RNA-RNA interactions to guide transcription factors to their target sites. Such in trans activity of ncRNAs could potentially enhance the binding specificity of transcription factors by providing an additional attachment site on top of the binding motifs recognized by transcription factors. Combining RNA techniques with chromatin methodology, our lab is focusing on elaborating on this novel mechanistic aspect of transcription factor recruitment. Our studies aim to further categorize the many ncRNAs that have not yet been ascribed an apparent function.