Determining the role of the long non-coding RNA HOTTIP in regulation of the HOXA gene cluster

Project Summary/Abstract Most transcription occurring in the human genome produces RNAs that do not encode proteins, and disruption of these non-coding RNAs (ncRNAs) is associated with multiple cancers. It is necessary to fully understand the role ncRNAs play in disease so that treatments and medicines can be developed. This project studies a particular ncRNA called HOTTIP which controls the expression of HOXA genes during the development of limbs. HOTTIP recruits the histone methyltransferase MLL1 to HOXA genes, however the mechanism of recruitment is unclear. By understanding how HOTTIP functions as a regulatory molecule, we can improve our knowledge of ncRNAs generally and identify ways to target ncRNAs therapeutically. This project involves creating a new technology through molecular engineering to determine the role of HOTTIP rapidly and confidently in human cells. It will be possible to uncover the exact way HOTTIP interacts with the MLL1 complex, and the degree the RNA molecule of HOTTIP itself is central to regulation of HOXA genes. This technology can then be used to study the thousands of other ncRNAs found in the human genome.