Integrative analysis unveils new functions for the Cutoff protein in noncoding RNA biogenesis and gene regulation.

TitleIntegrative analysis unveils new functions for the Cutoff protein in noncoding RNA biogenesis and gene regulation.
Publication TypeJournal Article
Year of Publication2017
AuthorsPritykin, Y, Brito, T, Schüpbach, T, Singh, M, Pane, A
Date Published2017 Jul
KeywordsAnimals, Chromatin Immunoprecipitation, DNA Transposable Elements, Drosophila melanogaster, Drosophila Proteins, Female, Gene Expression Regulation, Gene Expression Regulation, Developmental, Mutation, Ovary, RNA, Small Interfering, RNA, Untranslated, RNA-Binding Proteins, Sequence Analysis, RNA

<p>Piwi-interacting RNAs (piRNAs) are central components of the piRNA pathway, which directs transposon silencing and guarantees genome integrity in the germ cells of several metazoans. In , piRNAs are produced from discrete regions of the genome termed piRNA clusters, whose expression relies on the RDC complex comprised of the core proteins Rhino, Deadlock, and Cutoff. To date, the RDC complex has been exclusively implicated in the regulation of the piRNA loci. Here we further elucidate the function of Cutoff and the RDC complex by performing genome-wide ChIP-seq and RNA-seq assays in the ovaries and analyzing these data together with other publicly available data sets. In agreement with previous studies, we confirm that Cutoff is involved in the transcriptional regulation of piRNA clusters and in the repression of transposable elements in germ cells. Surprisingly, however, we find that Cutoff is enriched at and affects the expression of other noncoding RNAs, including spliceosomal RNAs (snRNAs) and small nucleolar RNAs (snoRNAs). At least in some instances, Cutoff appears to act at a transcriptional level in concert with Rhino and perhaps Deadlock. Finally, we show that mutations in Cutoff result in the deregulation of hundreds of protein-coding genes in germ cells. Our study uncovers a broader function for the RDC complex in the germline development.</p>

Alternate JournalRNA
PubMed ID28420675
PubMed Central IDPMC5473144
Grant ListR01 GM076275 / GM / NIGMS NIH HHS / United States
R01 GM077620 / GM / NIGMS NIH HHS / United States
/ HHMI / Howard Hughes Medical Institute / United States