title: RNA-seq reveals post-transcriptional regulation of Drosophila insulin-like peptide dilp8 and the neuropeptide-like precursor Nplp2 by the exoribonuclease Pacman/XRN1.
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 coordinate 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.
authors.affiliation: Medical Research Building, Brighton and Sussex Medical School, University of Sussex, Falmer, Brighton BN1 9PS, UK.
authors.forename: Christopher I
authors.identifier: http://orcid.org/0000-0001-7065-1157
authors.initials: CI
authors.lastname: Jones
authors.affiliation: Medical Research Building, Brighton and Sussex Medical School, University of Sussex, Falmer, Brighton BN1 9PS, UK.
authors.forename: Amy L
authors.identifier: http://orcid.org/0000-0001-9241-8663
authors.initials: AL
authors.lastname: Pashler
authors.affiliation: Medical Research Building, Brighton and Sussex Medical School, University of Sussex, Falmer, Brighton BN1 9PS, UK.
authors.forename: Benjamin P
authors.identifier: http://orcid.org/0000-0001-7884-1131
authors.initials: BP
authors.lastname: Towler
authors.affiliation: Medical Research Building, Brighton and Sussex Medical School, University of Sussex, Falmer, Brighton BN1 9PS, UK.
authors.forename: Sophie R
authors.initials: SR
authors.lastname: Robinson
authors.affiliation: Medical Research Building, Brighton and Sussex Medical School, University of Sussex, Falmer, Brighton BN1 9PS, UK s.newbury@bsms.ac.uk.
authors.forename: Sarah F
authors.initials: SF
authors.lastname: Newbury
mesh_terms: D000483:Alleles; D000818:Animals; D004330:Drosophila / Q000235:genetics* / Q000378:metabolism*; D029721:Drosophila Proteins / Q000235:genetics* / Q000378:metabolism; D005095:Exoribonucleases / Q000378:metabolism*; D005786:Gene Expression Regulation; D055786:Gene Knockout Techniques; D063990:Gene Ontology; D018390:Gene Targeting; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics* / Q000378:metabolism; D009154:Mutation; D014176:Protein Biosynthesis; D012323:RNA Processing, Post-Transcriptional
chemical_list: D029721:Drosophila Proteins; D036341:Intercellular Signaling Peptides and Proteins; C572149:insulin-like peptide 8, Drosophila; D005095:Exoribonucleases; C487208:pcm protein, Drosophila