The stunning diversity of cellular form and function arising from identical genetic material is largely a result of which genes are expressed and at what levels. Historically, the study of gene expression has focused on protein-coding genes, however, we now know that some noncoding RNA genes can have regulatory functions. The Kleaveland lab is fascinated by these regulatory noncoding RNAs—what they do, how they do it, and how they impact mammalian development and disease.
Previously, we described an unusual network centered on four conserved RNAs—the Cyrano long noncoding RNA, the Cdr1as circular RNA, and the miR-7 and miR-671 microRNAs—that regulate each other in the mammalian brain (Kleaveland et al., Cell 2018). Building on that discovery, we are currently focused on the following three areas: 1) the molecular, cellular, and physiologic functions of this network, 2) the mechanisms and scope of microRNA degradation (e.g. Shi et al., Science 2020) and 3) the post-transcriptional regulation of circular RNAs. Leveraging the reagents and methods that we develop to study a few RNAs, we aspire to deorphan the functions of many regulatory RNAs and determine their contributions to human health.
- Functions of noncoding RNA networks
- Mechanism and scope of target-directed microRNA degradation
- Regulation of circular RNAs