Tis11 mediated mRNA degradation regulates intestinal stem cell quiescence in Drosophila melanogaster

we show that Tis11, an Adenine-uridine Rich Element (ARE) binding protein that promotes mRNA degradation, is required to re-establish basal proliferation rates of adult Drosophila intestinal stem cells (ISC) after a regenerative episode. We find that Tis11 limits ISC proliferation specifically after proliferation has been stimulated in response to heat stress or infection, and show that Tis11 expression and activity are increased in ISCs during tissue repair. Based on stem cell transcriptome analysis and RNA immunoprecipitation, we propose that Tis11 activation represents an integral part of a negative feedback mechanism that limits the expression of key components of several signaling pathways that control ISC function and proliferation. Our results identify Tis11 mediated mRNA decay as an evolutionarily conserved mechanism of re-establishing basal proliferation rates of stem cells in regenerating tissues. stem cell transcriptome analysis of sorted Drosphila ISC (control, Tis11 gain-of-function and Tis11 loss-of-function) and RNA immunoprecipitation of FLAG- tagged Tis11 bound mRNAs (FLAG-Tis11 expressed specifically in ISCs) performed in duplicate (control IgG precipitation and FLAG precipitiation)