Tankyrase-1 regulates RBP-mediated mRNA turnover to promote muscle fiber formation

Souad Mubaid, Brenda Janice Sanchez, Rinad A. Algehani, Viktoriia Skopenkova, Pauline Adjibade, Derek T. Hall, Sandrine Busque, Xian Jin Lian, Kholoud Ashour, Anne Marie K. Tremblay, Graeme Carlile, Jean Philippe Gagné, Andrea Diaz-Gaxiola, Shahryar Khattak, Sergio Di Marco, David Y. Thomas, Guy G. Poirier, Imed Eddine Gallouzi*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

4 Scopus citations

Abstract

Poly(ADP-ribosylation) (PARylation) is a post-translational modification mediated by a subset of ADP-ribosyl transferases (ARTs). Although PARylation-inhibition based therapies are considered as an avenue to combat debilitating diseases such as cancer and myopathies, the role of this modification in physiological processes such as cell differentiation remains unclear. Here, we show that Tankyrase1 (TNKS1), a PARylating ART, plays a major role in myogenesis, a vital process known to drive muscle fiber formation and regeneration. Although all bona fide PARPs are expressed in muscle cells, experiments using siRNA-mediated knockdown or pharmacological inhibition show that TNKS1 is the enzyme responsible of catalyzing PARylation during myogenesis. Via this activity, TNKS1 controls the turnover of mRNAs encoding myogenic regulatory factors such as nucleophosmin (NPM) and myogenin. TNKS1 mediates these effects by targeting RNA-binding proteins such as Human Antigen R (HuR). HuR harbors a conserved TNKS-binding motif (TBM), the mutation of which not only prevents the association of HuR with TNKS1 and its PARylation, but also precludes HuR from regulating the turnover of NPM and myogenin mRNAs as well as from promoting myogenesis. Therefore, our data uncover a new role for TNKS1 as a key modulator of RBP-mediated post-transcriptional events required for vital processes such as myogenesis.

Original languageEnglish (US)
Pages (from-to)4002-4020
Number of pages19
JournalNUCLEIC ACIDS RESEARCH
Volume52
Issue number7
DOIs
StatePublished - Apr 24 2024

ASJC Scopus subject areas

  • Genetics

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