RNA Biology Program
The central dogma of genetics is that DNA is transcribed to RNA, which is translated into proteins. RNA does a lot more than simply act as a messenger between our DNA and the ribosomes that make proteins. The nucleic acid plays a role in controlling which genes are turned on or off, a process that could have a profound impact on human health. But despite the importance of RNA in biology and medicine, little is known about the molecular and cellular mechanisms underlying RNA-based gene regulation in humans. Sanford-Burnham's RNA Biology program calls this function the "RNA Code," and is seeking to understand it.
The human genome contains about 22,000 protein-coding genes, far less than expected for such a complex organism. With this limited genetic framework, it is not surprising that humans have evolved complex RNA-based genetic and epigenetic regulations. In fact, the human genome contains tens of thousands of RNA sequences that do not translate into proteins. Instead, these RNA help regulate gene expression at transcriptional, co-transcriptional and post-transcriptional levels.
One class of the non-coding small RNAs is called microRNAs which are ~22 nucleotide single-stranded RNAs associated with a protein complex called the RNA-induced silencing complex (RISC) and dictate gene repression by base-pairing to mRNA of protein-coding genes in plant and animal cells. “Because these small RNAs regulate gene expression, they represent another switch we can use to understand and control disease,” says Professor and RNA Biology Program Director Tariq Rana, Ph.D. “For example, a number of disease sates including cancer can result when microRNAs are dysregulated by various mechanisms. But we need to understand the regulation of these mechanisms.”
RNA-based gene silencing is involved in almost every aspect of biology, including development, stem cell biology, disease progression and pathogenesis, immunity, inflammation and cancer. It is our hope that cracking the RNA Code will lead to advances in treating a host of diseases.