The laboratory has historically investigated small RNA biosynthetic pathways in yeast and human systems, including transcription, RNA processing, catalytic RNA, therapeutic RNAs, and in vitro evolution of RNA and DNA ligands. We are currently exploring these questions:
 Many genes and highly repetitive DNA elements encoding small RNAs not only produce functional RNA products, but have evolved to affect the spatial organization and regulation of the surrounding chromosomes. In particular, tRNA genes and SINE elements are distributed throughout the linear genome, but tend to cluster in three dimensions and to serve as both boundary elements and silencers though changes in local chromatin.
 RNase P is an ancient endonuclease containing a catalytic RNA subunit. In eukaryotes the enzyme has evolved into multiple forms with a far more complex complement of protein subunits that allow it to participate in several nuclear and cytoplasmic pathways for biosynthesis and turnover of pre-tRNAs, pre-mRNAs, lncRNAs and mRNAs.
 It has long been possible to create large random-sequence libraries of DNA, RNA, and modified RNA, from which highly specific ""aptamer"" ligands can be selected by a process that is variously called ""SELEX"" and ""in vitro evolution"". These ligands have many advantages over the creation of polyclonal and monoclonal antibodies, and aptamers for several experimental, diagnostic and therapeutic applications have been created and are in progress."
Pai, DA and Engelke, DR. Spatial organization of genes as a component of regulated expression. Chromosoma 119:13-25, 2010, PMC2809799
Srisawat, C and Engelke, DR. Selection of RNA aptamers that bind HIV-1 LTR DNA: strand invaders. Nucl. Acids. Res. 38: 8306-8315. 2010, PMC3001068
Marvin, MC, Walker, SC, Fierke, CA and Engelke, DR. Binding and cleavage of unstructured RNA by nuclear RNase P. RNA, 1429-1440, 2011, PMC3153968
Marvin, MC, Clauder-MÃ_nster, S, Walker, SC, Sarkeshik, A, Yates III, JR, Steinmetz, LM, and Engelke, DR. Accumulation of noncoding RNA due to an RNase P defect in Saccharomyces cerevisiae. RNA, epub, 2011, PMC3153968
Rodley*, CDM, Pai*, DA, Mills, TA, Engelke, DR, and Oâ€™Sullivan, JM (2011) tRNA gene identity affects nuclear positioning. PLoS ONE, 2011;6(12):e29267. (* = equal contribution). PMC3242769