IMP dehydrogenase type 1 associates with polyribosomes translating rhodopsin mRNA.
IMP dehydrogenase (IMPDH) catalyzes the pivotal step in guanine nucleotide biosynthesis. Here we show that both IMPDH type 1 (IMPDH1) and IMPDH type 2 are associated with polyribosomes, suggesting that these housekeeping proteins have an unanticipated role in translation regulation. This interaction is mediated by the subdomain, a region of disputed function that is the site of mutations that cause retinal degeneration. The retinal isoforms of IMPDH1 also associate with polyribosomes. The most common disease-causing mutation, D226N, disrupts the polyribosome association of at least one retinal IMPDH1 isoform. Finally, we find that IMPDH1 is associated with polyribosomes containing rhodopsin mRNA. Because any perturbation of rhodopsin expression can trigger apoptosis in photoreceptor cells, these observations suggest a likely pathological mechanism for IMPDH1-mediated hereditary blindness. We propose that IMPDH coordinates the translation of a set of mRNAs, perhaps by modulating localization or degradation.
Mortimer
Sarah E
SE
Department of Biochemistry, Brandeis University, Waltham, Massachusetts 02454-9110, USA.
Xu
Dong
D
McGrew
Dharia
D
Hamaguchi
Nobuko
N
Lim
Hoong Chuin
HC
Bowne
Sara J
SJ
Daiger
Stephen P
SP
Hedstrom
Lizbeth
L
D000818:Animals; D020134:Catalytic Domain; D002417:Cattle; D049109:Cell Proliferation; D006367:HeLa Cells; D006801:Humans; D007168:IMP Dehydrogenase / Q000378:metabolism / Q000502:physiology*; D008954:Models, Biological; D008968:Molecular Conformation; D009154:Mutation; D011132:Polyribosomes / Q000737:chemistry; D020033:Protein Isoforms; D012160:Retina / Q000378:metabolism; D012243:Rhodopsin / Q000378:metabolism*; D012270:Ribosomes / Q000378:metabolism*
D020033:Protein Isoforms; D012243:Rhodopsin; D007168:IMP Dehydrogenase