Maternally inherited stable intronic sequence RNA triggers a self-reinforcing feedback loop during development

Abstract

Summary Maternally inherited noncoding RNAs (ncRNAs) can regulate zygotic gene expression across generations [1–4]. Recently, many stable intronic sequence RNAs (sisRNAs), which are byproducts of pre-mRNA splicing, were found to be maternally deposited and persist till zygotic transcription in Xenopus and Drosophila [5–7]. In various organisms, sisRNAs can be in linear or circular conformations, and they have been suggested to regulate host gene expression [5–10]. It is unknown whether maternally deposited sisRNAs can regulate zygotic gene expression in the embryos. Here, we show that a maternally inherited sisRNA ( sisR-4 ) from the deadpan locus is important for embryonic development in Drosophila . Mothers, but not fathers, mutant for sisR-4 produce embryos that fail to hatch. During embryogenesis, sisR-4 promotes transcription of its host gene ( deadpan ), which is essential for development. Interestingly, sisR-4 functions by activating an enhancer present in the intron where sisR-4 is encoded. We propose that a maternal sisRNA triggers expression of its host gene via a positive feedback loop during embryogenesis.