Shannon Lauberth
The role of noncoding RNAs and RNA binding proteins in cancer: shedding light on the transcriptomic dark matter
Noncodingwn as downstream-of-gene (DoG) transcripts. Although DoG RNAs are increasingly recognized as markers of cellular stress—such as viral infection, heat shock, and osmotic stress—the mechanisms that govern their production and their impact on gene expression remain poorly understood.
RNAs (ncRNAs) play a crucial role in a wide array of functions related to development and disease, primarily through their regulation of transcription, RNA processing, and translation. Among the recently identified classes of long noncoding RNAs (lncRNAs) are transcripts found downstream of protein-coding gene boundaries, kno
In our recent work, we identified a novel class of unannotated DoG RNAs, which are expressed in a tissue-specific manner. These transcripts originate from genomic regions enriched with active enhancer marks, sharing similarities with enhancer-derived RNAs (eRNAs). We found that defects in RNA Polymerase II (RNAPII) termination, caused by the loss or inhibition of Topoisomerase I (TOP1), lead to enhanced DoG production. Based on this, we hypothesize that DoG RNAs play a role in the cellular stress response, helping to fine-tune transcriptional adjustments to environmental and transcriptional stressors.
Our research is also pioneering the discovery of RNA-binding proteins (RBPs), revealing new RNA binding sites and highlighting the critical roles of RNA in modulating chromatin and transcriptional regulation. Importantly, we uncovered a mechanism by which RNA influences DNA topology through interaction with the RNA-binding protein and enzyme Topoisomerase I (TOP1). This finding unveils a previously unexplored pathway through which RNA contributes to transcription-coupled topological stress, sparking interest in targeting RBPs for therapeutic interventions. We are currently exploring the RNA-binding interface of TOP1 as a promising target for drug development.
Our research is also pioneering the discovery of RNA-binding proteins (RBPs), revealing new RNA binding sites and highlighting the critical roles of RNA in modulating chromatin and transcriptional regulation. Importantly, we uncovered a mechanism by which RNA influences DNA topology through interaction with the RNA-binding protein and enzyme Topoisomerase I (TOP1). This finding unveils a previously unexplored pathway through which RNA contributes to transcription-coupled topological stress, sparking interest in targeting RBPs for therapeutic interventions. We are currently exploring the RNA-binding interface of TOP1 as a promising target for drug development.