RUFY4 exists as two translationally regulated isoforms, that localize to the mitochondrion in activated macrophages

Abstract

We report here that RUFY4, a newly characterized member of the ‘RUN and FYVE domain-containing’ family of proteins previously associated with autophagy enhancement, is highly expressed in alveolar macrophages (AM). We show that RUFY4 interacts with mitochondria upon stimulation by microbial-associated molecular patterns of AM and dendritic cells. RUFY4 interaction with mitochondria and other organelles is dependent on a previously uncharacterized OmpH domain located immediately upstream of its C-terminal FYVE domain. Further, we demonstrate that rufy4 messenger RNA can be translated from an alternative translation initiation codon, giving rise to a N-terminally truncated form of the molecule lacking most of its RUN domain and with enhanced potential for its interaction with mitochondria. Our observations point towards a role of RUFY4 in selective mitochondria clearance in activated phagocytes.

Intravesical BCG in patients with non-muscle invasive bladder cancer induces trained immunity and decreases respiratory infections

“…Among those that were upregulated, we identified four genes involved in inflammasome activation: GBP1, AIM2, CASP5 and KCNMA1, 85 86 and one gene involved in positive regulation of autophagy: RUFY4 . 87–89 Interestingly, three genes coding for hemoglobin subunits ( HBA1 , HBA2 , HBB ) remained downregulated.…”

RUFY3 regulates endolysosomes perinuclear positioning, antigen presentation and migration in activated phagocytes

“…We identified RUFY3 and RUFY4, as two proteins highly expressed in bone marrow-derived dendritic cells (bmDCs), likely involved in the regulation of endosome and autophagosome dynamics in response to Interleukin-4 (IL-4) exposure or MAMPs detection 28 , 29 . Genomic databases interrogation indicates that the rufy3 mRNA is submitted to tissue dependent alternative splicing with 7 different transcripts detected in mouse.…”

Intravesical BCG in patients with non-muscle invasive bladder cancer induces trained immunity and decreases respiratory infections

“…A total of 26 genes remained upregulated at punadj<0.05 from BCG6 to pre-BCG7 and 27 genes remained downregulated (Supplementary Table 8). Among those that were upregulated, we identified four genes involved in inflammasome activation: GBP1, AIM2, CASP5 and KCNMA1 65, 66 , and one gene involved in positive regulation of autophagy: RUFY4 67–69 . Interestingly, three genes coding for hemoglobin subunits ( HBA1 , HBA2 , HBB ) remained downregulated.…”