RNA-seq reveals post-transcriptional regulation of Drosophila insulin-like peptide dilp8 and the neuropeptide-like precursor Nplp2 by the exoribonuclease Pacman/XRN1

Jones, Christopher I, Pashler, Amy L, Towler, Benjamin P, Robinson, Sophie R and Newbury, Sarah F (2016) RNA-seq reveals post-transcriptional regulation of Drosophila insulin-like peptide dilp8 and the neuropeptide-like precursor Nplp2 by the exoribonuclease Pacman/XRN1. Nucleic Acids Research, 44 (1). pp. 267-280. ISSN 0305-1048

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Abstract

Ribonucleases are critically important in many cellular and developmental processes and defects in their expression are associated with human disease. Pacman/XRN1 is a highly conserved cytoplasmic exoribonuclease which degrades RNAs in a 5' - 3' direction. In Drosophila, null mutations in pacman result in small imaginal discs, a delay in onset of pupariation and lethality during the early pupal stage. In this paper, we have used RNA-seq in a genome-wide search for mRNAs misregulated in pacman null wing imaginal discs. Only 4.2% of genes are misregulated ±>2-fold in pacman null mutants compared to controls, in line with previous work showing that Pacman has specificity for particular mRNAs. Further analysis of the most upregulated mRNAs showed that Pacman post-transcriptionally regulates the expression of the secreted insulin-like peptide Dilp8. Dilp8 is related to human IGF-1, and has been shown to co-ordinate tissue growth with developmental timing in Drosophila. The increased expression of Dilp8 is consistent with the developmental delay seen in pacman null mutants. Our analysis, together with our previous results, show that the normal role of this exoribonuclease in imaginal discs is to suppress the expression of transcripts that are crucial in apoptosis and growth control during normal development.

Item Type: Article
Keywords: RNA stability, microRNAs, Drosophila, development, RNA-seq
Schools and Departments: Brighton and Sussex Medical School > Brighton and Sussex Medical School
Subjects: Q Science > QH Natural history > QH0301 Biology > QH0426 Genetics
Q Science > QH Natural history > QH0301 Biology > QH0426 Genetics > QH0447 Genes. Alleles. Genome
Q Science > QL Zoology > QL0360 Invertebrates > QL0434 Arthropoda > QL0463 Insects > QL0531 Diptera (Flies)
Q Science > QP Physiology > QP0501 Animal biochemistry
Depositing User: Sarah Newbury
Date Deposited: 12 Jan 2016 12:38
Last Modified: 07 Mar 2017 10:55
URI: http://sro.sussex.ac.uk/id/eprint/59107

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Project NameSussex Project NumberFunderFunder Ref
Epigenetic regulation of gene expression by the exoribonuclease pacmanG0056BBSRC-BIOTECHNOLOGY & BIOLOGICAL SCIENCES RESEARCH COUNCILBB/I021345/1
Studentship - TowlerWC003-11BSMSWC003-11
Studentship - RobinsonWC003-14BSMSWC003-14