Stress-sensitive dynamics of miRNAs and Elba1 in Drosophila embryogenesis

Exposures to stress during development can have long-term consequences for the upcoming adult phenotype. However, the timing of the exposure is crucial to achieve such abiding effects. Using the wm4h Drosophila melanogaster strain, we found that heat shock applied during the first hour of embryogenesis, before stable heterochromatin formation and zygotic independence, had long-term loss of silencing of the position-effect variegation reporter white.Since small non-coding RNAs (sncRNAs) are suggested as important carriers of epigenetic information, we carefully established a sncRNA timeline using high throughput sequencing for the first 5 embryonic stages of Drosophila embryogenesis. We found that the sncRNA-profile during this period is accompanied by rapid temporal changes with the most striking effects found within the miRNA family.We further examined the sncRNA profiles in cellularized stage 5 single embryos and found that heat shock induced upregulation of a specific group of miRNA, including some of maternal origin. These would, under normal conditions, be degraded during the maternal to zygotic transition occurring before cellularization. Using RNA extracts from the same embryos, we also sequenced long RNA and found an inverse correlation between those miRNAs and significantly down-regulated early zygotic non-paused pre-midblastula genes. One of these genes, Elba1, is an insulator binding factor specifically expressed during this developmental window. Critically, genes that were involved in developmental processes and overexpressed in response to heat shock overlap with Elba1-binding regions, supporting a heat shock sensitive miRNA-Elba1 axis in regulating the first zygotic transcriptome, developmental speed and affecting the first chromatin environment.