PLoS ONE (Jan 2021)

Cell-cell adhesion regulates Merlin/NF2 interaction with the PAF complex.

  • Anne E Roehrig,
  • Kristina Klupsch,
  • Juan A Oses-Prieto,
  • Selim Chaib,
  • Stephen Henderson,
  • Warren Emmett,
  • Lucy C Young,
  • Silvia Surinova,
  • Andreas Blees,
  • Anett Pfeiffer,
  • Maha Tijani,
  • Fabian Brunk,
  • Nicole Hartig,
  • Marta Muñoz-Alegre,
  • Alexander Hergovich,
  • Barbara H Jennings,
  • Alma L Burlingame,
  • Pablo Rodriguez-Viciana

DOI
https://doi.org/10.1371/journal.pone.0254697
Journal volume & issue
Vol. 16, no. 8
p. e0254697

Abstract

Read online

The PAF complex (PAFC) coordinates transcription elongation and mRNA processing and its CDC73/parafibromin subunit functions as a tumour suppressor. The NF2/Merlin tumour suppressor functions both at the cell cortex and nucleus and is a key mediator of contact inhibition but the molecular mechanisms remain unclear. In this study we have used affinity proteomics to identify novel Merlin interacting proteins and show that Merlin forms a complex with multiple proteins involved in RNA processing including the PAFC and the CHD1 chromatin remodeller. Tumour-derived inactivating mutations in both Merlin and the CDC73 PAFC subunit mutually disrupt their interaction and growth suppression by Merlin requires CDC73. Merlin interacts with the PAFC in a cell density-dependent manner and we identify a role for FAT cadherins in regulating the Merlin-PAFC interaction. Our results suggest that in addition to its function within the Hippo pathway, Merlin is part of a tumour suppressor network regulated by cell-cell adhesion which coordinates post-initiation steps of the transcription cycle of genes mediating contact inhibition.