Loss of the Integrator and Nuclear Exosome Targeting complexes disrupts oogenesis and causes the emergenceof atypical transcripts in Drosophila

Abstract

Nuclear RNA homeostasis depends on the balance of transcription, RNA processing, degradation, and transport between the nucleus and cytoplasm. RNA degradation directed by the Integrator, nuclear exosome targeting (NEXT), and nuclear exosome complexes controls the accumulation of aberrant nuclear RNA. Here, we report that Drosophila oogenesis requires the Integrator, NEXT, and nuclear exosome complexes. Depletion of Integrator, NEXT, or nuclear exosome components in Drosophila female germ cells causes infertility and accumulation of 3' extended snRNAs, promoter upstream transcripts (PROMPTs), and cryptic transcripts. Our data highlight the essential role of nuclear RNA degradation and processing in Drosophila oogenesis and provide a catalog of RNAs whose nuclear levels are regulated by these three complexes. We propose that Integrator, NEXT, and the nuclear exosome support oogenesis by ensuring that inappropriate transcription does not overwhelm the limited supply of proteins that bind, process, and traffic RNA.