PAPγ associates with PAXT nuclear exosome to control the abundance of PROMPT ncRNAs

Xavier Contreras, David Depierre, Charbel Akkawi, Marina Srbic, Marion Helsmoortel, Maguelone Nogaret, Matthieu LeHars, Kader Salifou, Alexandre Heurteau, Olivier Cuvier and Rosemary Kiernan ()
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Xavier Contreras: Institute of Human Genetics (IGH)/University of Montpellier, Gene Regulation Lab
David Depierre: University of Toulouse
Charbel Akkawi: Institute of Human Genetics (IGH)/University of Montpellier, Gene Regulation Lab
Marina Srbic: Institute of Human Genetics (IGH)/University of Montpellier, Gene Regulation Lab
Marion Helsmoortel: Institute of Human Genetics (IGH)/University of Montpellier, Gene Regulation Lab
Maguelone Nogaret: Institute of Human Genetics (IGH)/University of Montpellier, Gene Regulation Lab
Matthieu LeHars: Institute of Human Genetics (IGH)/University of Montpellier, Gene Regulation Lab
Kader Salifou: Institute of Human Genetics (IGH)/University of Montpellier, Gene Regulation Lab
Alexandre Heurteau: University of Toulouse
Olivier Cuvier: University of Toulouse
Rosemary Kiernan: Institute of Human Genetics (IGH)/University of Montpellier, Gene Regulation Lab

Nature Communications, 2023, vol. 14, issue 1, 1-14

Abstract: Abstract Pervasive transcription of the human genome generates an abundance of RNAs that must be processed and degraded. The nuclear RNA exosome is the main RNA degradation machinery in the nucleus. However, nuclear exosome must be recruited to its substrates by targeting complexes, such as NEXT or PAXT. By proteomic analysis, we identify additional subunits of PAXT, including many orthologs of MTREC found in S. pombe. In particular, we show that polyA polymerase gamma (PAPγ) associates with PAXT. Genome-wide mapping of the binding sites of ZFC3H1, RBM27 and PAPγ shows that PAXT is recruited to the TSS of hundreds of genes. Loss of ZFC3H1 abolishes recruitment of PAXT subunits including PAPγ to TSSs and concomitantly increases the abundance of PROMPTs at the same sites. Moreover, PAPγ, as well as MTR4 and ZFC3H1, is implicated in the polyadenylation of PROMPTs. Our results thus provide key insights into the direct targeting of PROMPT ncRNAs by PAXT at their genomic sites.

Date: 2023
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DOI: 10.1038/s41467-023-42620-9

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