m6A RNA modification in Drosophila: a new way to fine tune gene expression
University of Lausanne, Switzerland
In recent years it has become evident that the transcriptome is extensively and dynamically altered by a variety of RNA modifications, which – similar to post-translational modifications - harbor the potential of altering RNA fate and, in turn, regulating cellular physiology. N6-methyladenosine RNA (m6A) is among the most abundant mRNA modifications in vertebrates that regulates most mRNA processing steps and is involved in several biological processes, including circadian clock, metabolism and embryonic stem cell differentiation. However, its precise roles during development of complex organisms remain unclear. We carried out a comprehensive molecular and physiological characterization of the individual component of the m6A methyltransferase complex as well as of the reader proteins in Drosophila melanogaster. Components of the complex are ubiquitously expressed with clear enrichment in the nervous system. Consistently, mutant flies for the catalytic subunits suffer from severe locomotion defects due to impaired neuronal functions. Components of the m6A methyltransferase complex also fine-tune the female-specific splicing of Sex lethal (Sxl) transcript and of its downstream targets, revealing a role for this modification in sex determination and dosage compensation. I will present our current data regarding the roles of writer and reader proteins in these m6A-dependent RNA processes in Drosophila.