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RNA. 2017 Jul;23(7):1097-1109. doi: 10.1261/rna.058594.116. Epub 2017 Apr 18.

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

Author information

1
The Lewis-Sigler Institute for Integrative Genomics, Princeton University, Princeton, New Jersey 08544, USA.
2
Department of Computer Science, Princeton University, Princeton, New Jersey 08544, USA.
3
Computational and Systems Biology Program, Memorial Sloan Kettering Cancer Center, New York, New York 10065, USA.
4
Instituto de Ciências Biomédicas (ICB), Universidade Federal do Rio de Janeiro (UFRJ), Rio de Janeiro 21949-902, Brazil.
5
Department of Molecular Biology, Princeton University, Princeton, New Jersey 08544, USA.

Abstract

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 Drosophila, 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 Drosophila 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 Drosophila germline development.

KEYWORDS:

Cutoff; Drosophila; germline; noncoding RNAs; piRNAs

PMID:
28420675
PMCID:
PMC5473144
DOI:
10.1261/rna.058594.116
[Indexed for MEDLINE]
Free PMC Article

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