Collaborative Research: Nucleobase-Modified Peptide Nucleic Acid (PNA) for Sequence Selective Triple-Helical Recognition of Non-Coding Ribonucleic Acid (RNA)

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With this award, the Chemistry of Life Processes Program in the Chemistry Division is funding a collaborative effort between Professors Eriks Rozners (Binghamton University) and James A. MacKay (Elizabethtown College). The research develops new methods for molecular recognition of biologically-significant, non-coding ribonucleic acid (RNA). The majority of cellular RNA consists of non-coding RNAs that play important roles in regulating gene expression even though these processes are not fully understood. Selective recognition, imaging, and functional regulation of such RNAs are useful for fundamental studies and practical applications in biotechnology. The project expands interdisciplinary, collaborative research across traditional institutional boundaries. The project establishes a bridge for Elizabethtown College (a primarily undergraduate institution) students to transition from undergraduate studies to advanced graduate studies at a research university. Undergraduate students, especially women, minorities and first generation college students, participate in the project. The project also contributes to improving STEM education. The development of sequence selective RNA binders is important for understanding the biochemistry of non-coding RNAs. Such binders may impact fundamental RNA biology and practical applications in biotechnology and synthetic biology. This collaborative study is developing new peptide nucleic acid (PNA) nucleobases that enable recognition of the entire Hoogsteen face of Watson-Crick and non-canonical base pairs of double-stranded RNA. The properties of the novel nucleobases are optimized using synthetic organic chemistry to enable recognition of any sequence of double-stranded RNA. This approach may solve a long-standing problem in molecular recognition of RNA and enables a variety of applications. Examples of such applications are: imaging and functional control of regulatory RNA, designer riboswitches for synthetic biology, and inhibition of biologically-important RNA for fundamental studies.