Final Report Summary - RNA-MAPS (Uncovering and understanding RNA through Massively Parallel Sequencing)
The unfolding of the instructions encoded in the genome is triggered by the transcription of DNA into RNA (the expression of the genes), and the subsequent processing of the resulting primary RNA transcripts into functional mature RNAs. Within an organism, the regulated production of RNA leads to an extraordinary diversity of functions and morphologies across billions of cells that share essentially the same genome sequence. The population of all RNAs in the cell is thus the first phenotypic manifestation of the genome, and at the same time, the determinant of the higher order phenotypes of the cell, mediating necessarily all phenotypic changes at the organism level caused by changes in the DNA sequence. However, the mechanisms that underlie cellular fates upon differentiation and development are still poorly understood. The RNA-MAPS project aims to the understanding of the genetic and epigenetic factors responsible for the regulation gene expression and RNA processing during differentiation and development. Towards that aim, we have specifically studied two dynamic processes: the transdifferentiation from human proB cells into functional macrophages and the differentiation and development of Drosophila melanogaster tissues. We have obtained an unprecedented data set on the temporal dynamics of gene expression, from DNA to RNA to proteins. Analysis of these data is contributing enormously to the understanding of the regulatory mechanisms underlying cell differentiation.