The catalytic-dead Pcif1 regulates gene expression and fertility in Drosophila

Article Article scientifique Article The catalytic-dead Pcif1 regulates gene expression and fertility in Drosophila eng 2023-02-08 2023-05-08 author Franco Giulia 0000-0002-4833-1330 803128 author Taillebourg Emmanuel 0000-0002-9328-6997 author Delfino Elena 0000-0002-6466-5058 916138 Département de biologie moléculaire et cellulaire (MOCEL) author Homolka David 0000-0002-6662-3409 856314 Département de biologie moléculaire et cellulaire (MOCEL) author Gueguen Nathalie author Brasset Emilie 0000-0003-2479-7969 author Pandey Radha Raman 0000-0002-4439-8386 853296 author Pillai Ramesh 0000-0003-2080-3604 854560 Département de biologie moléculaire et cellulaire (MOCEL) author Fauvarque Marie-Odile 0000-0001-5020-3701 609-619 10.1261/rna.079192.122 36754578 1355-8382 PMC10158991 http://rnajournal.cshlp.org/lookup/doi/10.1261/rna.079192.122 Eukaryotic mRNAs are modified at the 5′ end with a methylated guanosine (m 7 G) that is attached to the transcription start site (TSS) nucleotide. The TSS nucleotide is 2′- O -methylated (Nm) by CMTR1 in organisms ranging from insects to human. In mammals, the TSS adenosine can be further N 6 -methylated by RNA polymerase II phosphorylated CTD-interacting factor 1 (PCIF1) to create m 6 Am. Curiously, the fly ortholog of mammalian PCIF1 is demonstrated to be catalytic-dead, and its functions are not known. Here, we show that Pcif1 mutant flies display a reduced fertility which is particularly marked in females. Deep sequencing analysis of Pcif1 mutant ovaries revealed transcriptome changes with a notable increase in expression of genes belonging to the mitochondrial ATP synthetase complex. Furthermore, the Pcif1 protein is distributed along euchromatic regions of polytene chromosomes, and the Pcif1 mutation behaved as a modifier of position-effect-variegation (PEV) suppressing the heterochromatin-dependent silencing of the white gene. Similar or stronger changes in the transcriptome and PEV phenotype were observed in flies that expressed a cytosolic version of Pcif1. These results point to a nuclear cotranscriptional gene regulatory role for the catalytic-dead fly Pcif1 that is probably based on its conserved ability to interact with the RNA polymerase II carboxy-terminal domain. N6-methyladenosine Pcif1 M6A M6Am Position-effect variegation (PEV) Transcription Dewey 570 French National Research Agency (ANR) Birth and Activation of a piRNA cluster ANR-21-CE12-0022 BiopiC FR French National Research Agency (ANR) CBH-EUR-GS ANR-17-EURE-0003 CBH-EUR-GS FR French National Research Agency (ANR) CHApiTRE : CHAracterization of piRNA cluster expression throughout development and their capacity to tame a sudden TRansposable Element activity ANR-20-CE12-0005 CHApiTRE FR 43 Département de biologie moléculaire 161 false RNA 29 5 067d0423-016c-495c-b24d-1f972e311fec Article (Published version) Public PILLAI010.pdf 4112797 application/pdf CC BY-NC-4.0 a8588c5901495b4572ffd5e1a94ada42f21dd0a62615e61f979d60fd785c2627 openAccess Faculté des sciences / Section de biologie / Département de biologie moléculaire

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The catalytic-dead Pcif1 regulates gene expression and fertility in Drosophila	RNA			2023	102	47

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Franco, Giulia