Abstract
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 midgestation 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. Coimmunoprecipitation revealed the close association of p32 with the mitoribosome. We propose that p32 is required for functional mitoribosome formation to synthesize proteins within mitochondria.
| Original language | English |
|---|---|
| Pages (from-to) | 9717-9737 |
| Number of pages | 21 |
| Journal | Nucleic Acids Research |
| Volume | 40 |
| Issue number | 19 |
| DOIs | |
| Publication status | Published - Oct 1 2012 |
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All Science Journal Classification (ASJC) codes
- Genetics
Cite this
P32/gC1qR is indispensable for fetal development and mitochondrial translation : Importance of its RNA-binding ability. / Yagi, Mikako; Uchiumi, Takeshi; Takazaki, Shinya; Okuno, Bungo; Nomura, Masatoshi; Yoshida, Shin Ichi; Kanki, Tomotake; Kang, Dongchon.
In: Nucleic Acids Research, Vol. 40, No. 19, 01.10.2012, p. 9717-9737.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - P32/gC1qR is indispensable for fetal development and mitochondrial translation
T2 - Importance of its RNA-binding ability
AU - Yagi, Mikako
AU - Uchiumi, Takeshi
AU - Takazaki, Shinya
AU - Okuno, Bungo
AU - Nomura, Masatoshi
AU - Yoshida, Shin Ichi
AU - Kanki, Tomotake
AU - Kang, Dongchon
PY - 2012/10/1
Y1 - 2012/10/1
N2 - 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 midgestation 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. Coimmunoprecipitation revealed the close association of p32 with the mitoribosome. We propose that p32 is required for functional mitoribosome formation to synthesize proteins within mitochondria.
AB - 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 midgestation 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. Coimmunoprecipitation revealed the close association of p32 with the mitoribosome. We propose that p32 is required for functional mitoribosome formation to synthesize proteins within mitochondria.
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U2 - 10.1093/nar/gks774
DO - 10.1093/nar/gks774
M3 - Article
VL - 40
SP - 9717
EP - 9737
JO - Nucleic Acids Research
JF - Nucleic Acids Research
SN - 0305-1048
IS - 19
ER -