Specific cleavage of RNA is critical for in vitro manipulation of RNA and in vivo gene silencing, yet sequence specific RNA endonucleases have not been identified in nature. We have engineered novel RNA endonucleases equivalent to the DNA restriction enzymes by combining a general RNA cleavage domain with a series of designed RNA binding domains (PUF domains) that specifically recognize different 8-nt RNA sequences. I will discuss the design of this novel enzyme, potential therapeutic application and RNA synthetic biology. Exponential advances in genomic technologies over the last decade have ushered in an explosion in our understanding of the transcriptional and mutational alterations in cancer, providing a “comprehensive portrait” of genomic alterations that was previously unimaginable. Defining a complete catalog of alterations in the alternative splicing as well as protein landscape in cancer is a principal component of completing this portrait. Now, it is established fact that RNA not only function as a messenger between DNA and protein but also involved in the regulation of genome organization and gene expression, which is immensely elaborate in complex organisms. My primary research goal is to understand RNA-protein interaction which has a role in modulating post transcriptional genome and therefore proteome. Modulation of activity of the proteins by post translational modification (PTM) further adds complexity to the RNA centric model. I propose a systemic study of alternative splicing and integration of post translational modulations in understanding molecular mechanism of carcinogenesis.