p32/gC1qR is indispensable for fetal development and mitochondrial translation: importance of its RNA-binding ability.
p32 is an evolutionarily conserved and ubiquitously expressed multifunctional protein. Although p32 exists at diverse intra and extracellular sites, it is predominantly localized to the mitochondrial matrix near the nucleoid associated with mitochondrial transcription factor A. Nonetheless, its function in the matrix is poorly understood. Here, we determined p32 function via generation of p32-knockout mice. p32-deficient mice exhibited mid-gestation lethality associated with a severe developmental defect of the embryo. Primary embryonic fibroblasts isolated from p32-knockout embryos showed severe dysfunction of the mitochondrial respiratory chain, because of severely impaired mitochondrial protein synthesis. Recombinant p32 binds RNA, not DNA, and endogenous p32 interacts with all mitochondrial messenger RNA species in vivo. The RNA-binding ability of p32 is well correlated with the mitochondrial translation. Co-immunoprecipitation revealed the close association of p32 with the mitoribosome. We propose that p32 is required for functional mitoribosome formation to synthesize proteins within mitochondria.
Department of Clinical Chemistry and Laboratory Medicine, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan.
Mikako
M
Yagi
Takeshi
T
Uchiumi
Shinya
S
Takazaki
Bungo
B
Okuno
Masatoshi
M
Nomura
Shin-ichi
S
Yoshida
Tomotake
T
Kanki
Dongchon
D
Kang
D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D002352:Carrier Proteins / Q000378:metabolism*; D049109:Cell Proliferation; D019069:Cell Respiration; D002478:Cells, Cultured; D004272:DNA, Mitochondrial / Q000032:analysis; D047109:Fetal Development; D005347:Fibroblasts / Q000378:metabolism; D005804:Genes, Lethal; D006367:HeLa Cells; D006801:Humans; D018960:Hyaluronan Receptors / Q000235:genetics / Q000502:physiology*; D053078:Membrane Potential, Mitochondrial; D051379:Mice; D018345:Mice, Knockout; D008928:Mitochondria / Q000235:genetics* / Q000378:metabolism / Q000648:ultrastructure; D024101:Mitochondrial Proteins / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D014176:Protein Biosynthesis; D012313:RNA / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D000077278:RNA, Mitochondrial; D016601:RNA-Binding Proteins / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D012270:Ribosomes / Q000378:metabolism
C087299:C1QBP protein, human; C490193:C1qbp protein, mouse; D002352:Carrier Proteins; D004272:DNA, Mitochondrial; D018960:Hyaluronan Receptors; D024101:Mitochondrial Proteins; D012333:RNA, Messenger; D000077278:RNA, Mitochondrial; D016601:RNA-Binding Proteins; D012313:RNA; D000255:Adenosine Triphosphate