UC Merced

Stem cell proliferation and differentiation is tightly regulated, and this balance is incredibly important for the health of an organism, especially in development of the central nervous system. N6-methyladenosine (m6A) is the most prevalent post-transcriptional mRNA modification in eukaryotes and has especially high levels in the Drosophila melanogaster central nervous system. However, the extent to which the m6A-modified transcriptome differs among cells of the nervous system and how m6A contributes to the metabolism of RNA in different cells remains to be seen.To address this gap in research, we have mapped the modification in neural progenitor cells and differentiated neurons using Drosophila larval brains. I used Drosophila genetics, cell type-specific mRNA decay measurements, m6A immunoprecipitation, and immunofluorescence to map m6A and determine its effects in each cell type. Here, I show that while m6A is rarely cell-type specific, mRNA decay is differentially regulated in these cells. m6A correlates with decreased mRNA stability in neuroblasts, but this cell type-specificity is likely due to m6A-independent stabilization of target transcripts in neurons. I propose a model in which the relationship between m6A and mRNA stability is not causal but rather is indicative of a compensatory mechanism in which m6A enhances translation of low stability mRNAs. This model is supported by in vivo quantitative imaging that shows m6A promotes target protein production in neuroblasts and neurons. My thesis work provides a rare view of the cell type-specific distribution and function of m6A. This work contributes to the general field of epitranscriptome research and further establishes the Drosophila larval brain as a useful model for answering fundamental questions about m6A.