Nara Lee, PhD

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 has been proposed to contribute to transcription regulation. How these ncRNAs function molecularly is the overarching question of the Lee lab.

Our lab studies ncRNAs from Epstein-Barr virus (EBV) called EBER1 (EBV-encoded RNA 1) and EBER2 as a model system. EBV is an oncogenic gamma-herpesvirus with a prevalence of over 90% in the human population and is associated with several types of cancers, such as lymphomas and carcinomas. Using next-generation sequencing-based technology, we have recently shown that EBER2 facilitates 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.

Since viruses often adopt existing mechanisms from their hosts, our observation suggests that as yet unknown cellular ncRNAs might exist that use RNA-RNA interactions to guide transcription factors to their target sites. By studying the molecular mechanism of EBERs in greater detail, we seek to extrapolate our findings to the host cell and identify functional cellular ncRNAs. To this end, we combine RNA techniques with chromatin methodology as well as refine existing tools to uncover the modes of action of ncRNAs.

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