RNA: Master or Servant?

Professor Karla Neugebauer
Dept of Molecular Biophysics & Biochemistry
Yale University

Abstract: RNA has sequence and structure that give it great versatility. It can expose side chains in single stranded regions for protein interaction or translation. It can hide in complicated stem loops. It can be catalytic. These are some of the properties that cause us to love RNA as a molecule. However well this is appreciated by the wider community of biologists, RNA is still viewed as a messenger racing barefoot between the realms of two great kings. Perhaps we have this unconscious bias about RNA, because these are the fairytales we grew up with. My lab studies RNA processing events localized on nascent RNA at sites of transcription (genes) as well as nuclear Cajal bodies, which are the assembly sites for RNA-protein complexes involved in splicing. Our findings lead us to ask: Is it possible that RNA has even greater capacity to organize cells than we have imagined already?

Bio: Karla Neugebauer holds a BS in Biology from Cornell University, where she worked with Miriam Salpeter on the development of the neuromuscular junction. She obtained her PhD in Neuroscience from UCSF, working with Louis Reichardt on cell adhesion molecules and integrins that promote growth cone motility and axon growth. She then switched gears to RNA biology, when she moved to a postdoc with Mark Roth at Fred Hutchinson Cancer Research Center. There she participated in the initial description of the SR protein family of splicing regulators and was inspired to study RNA metabolism in vivo by combining imaging, genomics, and sequencing strategies. Her lab has shown that snRNP assembly occurs in nuclear compartments, called Cajal bodies (CBs), and that depletion of the CB scaffolding protein coilin is lethal in zebrafish embryos, due to a deficit in splicing. Her lab has also discovered splicing-related pausing in last exons and has shown that splicing rates are tightly matched to transcription. The latter finding indicates that the spliceosome is in close proximity to Pol II during splicing, laying the groundwork for studies of regulation.