Modes of action of long noncoding RNAs

Our primary interest is in understanding the codes that are driving long noncoding RNA (lncRNA) functionality. Deciphering these codes is important, for example, for understanding the impact of mutations (that can now be effectively read with whole genome sequencing) on lncRNA function and for prioritizing variants that may have consequential impact. As lncRNA function remains poorly understood we're taking an integrated approach, which attempts to derive insights about lncRNA modes of action from the following sources:

• High throughput screens - using pooled high-throughput approaches, we are synthetizing and mutating in paralel tens of thousands of sites from various lncRNAs and testing which of the sites can carry out specific cellular and molecular function. (Lubelsky et al. Nature 2018)
• Detailed interrogation of specific lncRNAs - we are using synthetic constructs, reporter assays, and genome engineering to dissect the sequence and structure contribution to function in various lncRNAs studied in the lab. (e.g., NORAD Tichon et al. Nature Comms 2016, Tichon et al. Genes & Dev 2018, and Farberov et al. 2024)
• Comparative genomics - we are developing computational methods for identifying conserved sequence and structure elements in lncRNAs by comparing homologous lncRNA sequences from different species (Ross et al. Genome Biology 2020).