Doron Betel, MSKCC - Computational Biology Center, New York, NY, USA
Non coding RNAs (joint with Debora Marks)

Overall goal: stimulate interest in small RNA field, its history, to motivate students to solve puzzles of micro and siRNA gene regulation, using system and computational methodologies

The discovery of microRNAs and other silencing RNAs has revolutionized our understanding of post-transcriptional gene regulation. MicroRNAs act as negative regulators of gene expression, mostly by base pairing to the 3’UTRs and subsequent recruitment of a silencing complex. By analogous mechanism some organisms use short interfering RNAs (siRNA) to silence both foreign (viral defense) and self RNA. The importance of microRNAs is underscored by their ubiquitous presence in all sequences metazoans and their conservation across 500 million years of evolution. Each microRNAs can regulate hundreds of genes in a cell and inversely, many genes are regulated by more than one microRNA, making for a highly combinatoric and redundant regulatory system. Increasing amount of research in recent years has demonstrated that microRNAs are crucial for a wide range of cellular activities such as stem cell maintenance, cell proliferation, host-viral interaction and are implicated in a number of human diseases including cancer. Although we know some of the individual effects and targets of microRNAs in specific developmental stages or pathologies, their overall functions remain elusive. A primary and ongoing computational challenge is microRNA target prediction and quantifying their regulatory effect, both of which are crucial for understanding of microRNA/ siRNA function and for their potential therapeutic use. This course will cover key aspects of the biological function and computational challenges of short interfering RNAs including:

  1. The discovery of microRNAs and RNA interference. lin-4, let-7 and RNAi in plants. Numbers and conservation. How the two fields came together. - DSM
  2. MicroRNA and siRNA target prediction. Computational methods, resources and paradoxes –DSM/ DB
  3. Discovery of other non protein coding RNAs in eukaryotes and prokaryotes. DB
  4. Biogenesis of microRNAs - DB
  5. Known functions of microRNAs in physiology, disease, cancer –DB
  6. siRNAs, microRNAs and their inhibitors in functional genomics and therapy – DSM