Mapping RNA interactomes by sequencing

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DESCRIPTION (provided by applicant): RNA-RNA interactions are important components of gene regulatory networks. There is yet no technology to map the entire RNA-RNA interactome in cells or tissues. As a result, although personal genomes are being sequenced, our capabilities to interpret genomic functions and to predict phenotypic variation from genomic sequence remain limited. We desperately need high-throughput technologies to map the molecular networks in any person or tissue. Here, we propose to develop an extremely high-throughput technology to map RNA-RNA interactomes in vivo. The central idea is to convert molecular interactions into DNA sequences and then read out the interactions by DNA sequencing. The proposed RNA Hi-C technology is capable of mapping all protein- assisted RNA-RNA interactions in one assay. This new technology is expected to be generally applicable to analyze any cell types and tissues. We will use cell fate decisions in pre-implantation development as a driven biological question. The new technology will be applied to test two competing hypotheses. We expect the results to clarify a physical principle behind the earliest cell fate decision in mammals, and therefore offer unprecedented information regarding infertility, miscarriage, and birth defects.