The interactome of CLUH reveals its association to SPAG5 and its co-translational proximity to mitochondrial proteins.BACKGROUND
 CLUH is an RBP recognizing specifically mRNAs coding for mitochondrial proteins, but its precise molecular function and interacting partners remain undiscovered in mammals.


 Here we reveal for the first time CLUH interactome in mammalian cells.  Using both co-IP and BioID proximity-labeling approaches, we identify novel molecular partners interacting stably or transiently with CLUH in HCT116 cells and mouse embryonic stem cells.  We reveal stable RNA-independent interactions of CLUH with itself and with SPAG5 in cytosolic granular structures.  More importantly, we uncover an unexpected proximity of CLUH to mitochondrial proteins and their cognate mRNAs in the cytosol.  We show that this interaction occurs during the process of active translation and is dependent on CLUH TPR domain.


 Overall, through the analysis of CLUH interactome, our study sheds a new light on CLUH molecular function by revealing new partners and by highlighting its link to the translation and subcellular localization of some mRNAs coding for mitochondrial proteins.
CLUH
Using both co-IP and BioID proximity-labeling approaches, we identify novel molecular partners interacting stably or transiently with CLUH in HCT116 cells and mouse embryonic stem cells. 
BioID proximity-labeling approaches
Using both co-IP and BioID proximity-labeling approaches, we identify novel molecular partners interacting stably or transiently with CLUH in HCT116 cells and mouse embryonic stem cells. 
co-IP