A tissue-specific microRNA prevents cellular reprogramming by two master regulator transcription factors. Anna Lyuksyutova, Mark Krasnow. Dept Biochem, Stanford Univ, Stanford, CA.

   Direct cellular reprogramming converts one cell type to another, bypassing the pluripotent state usually required to assume a new cell fate. Some aspects of the process, such as tissue-specific variability in direct-reprogramming potential, are not well understood. Here, we examine the reprogramming potential of nine cell types in Drosophila melanogaster embryos. We find that two potent reprogramming factors, the master regulators Trachealess(Trh) and Eyeless(Ey), are selectively destroyed in differentiated muscle, thus blocking direct reprogramming in this tissue. An 8bp sequence element within their 3'UTR is necessary for this tissue-specific regulation. The 8bp sequence element is part of a predicted binding site for miR-190, a microRNA expressed in muscle. When Trh is expressed in muscle lacking miR-190, the trh mRNA is no longer destroyed. The importance of preventing inappropriate expression of powerful master regulator genes in differentiated tissues is underscored by the significant reduction in locomotion speed in larvae expressing Trh in their muscle. This is a novel aspect of developmental regulation where cells can protect themselves against transcriptional hijacking by specifically destroying potent transcription factors and making these cells refractory to potential reprogramming. .