LRPPRC is necessary for polyadenylation and coordination of translation of mitochondrial mRNAs

被引：252

作者：

Ruzzenente, Benedetta ^{[1
,2
]}

Metodiev, Metodi D. ^{[1
]}

Wredenberg, Anna ^{[1
]}

Bratic, Ana ^{[1
,3
]}

Park, Chan Bae ^{[4
]}

Camara, Yolanda ^{[5
,6
]}

Milenkovic, Dusanka ^{[1
]}

Zickermann, Volker ^{[7
]}

Wibom, Rolf ^{[3
]}

Hultenby, Kjell ^{[3
]}

Erdjument-Bromage, Hediye ^{[8
]}

Tempst, Paul ^{[8
]}

Brandt, Ulrich ^{[7
]}

Stewart, James B. ^{[1
]}

Gustafsson, Claes M. ^{[9
]}

Larsson, Nils-Goeran ^{[1
,3
]}

机构：

[1] Max Planck Inst Biol Ageing, Dept Mitochondrial Genet, D-50931 Cologne, Germany

[2] Univ Padua, Dept Biol, Padua, Italy

[3] Karolinska Inst, Dept Lab Med, Stockholm, Sweden

[4] Ajou Univ, Inst Med Sci, Sch Med, Suwon 441749, South Korea

[5] Hosp Univ Vall dHebron, Unitat Patol Mitocondrial, Inst Recerca, Barcelona, Spain

[6] Ctr Invest Biomed Red Enfermedades Raras CIBERER, Barcelona, Spain

[7] Goethe Univ Frankfurt, Mol Bioenerget Grp, Ctr Membrane Prote, Sch Med, Frankfurt, Germany

[8] Mem Sloan Kettering Canc Ctr, Program Mol Biol, New York, NY 10021 USA

[9] Univ Gothenburg, Inst Biomed, Gothenburg, Sweden

来源：

EMBO JOURNAL | 2012年 / 31卷 / 02期

基金：

瑞典研究理事会;

关键词：

Leigh syndrome French Canadian variant; LRPPRC; mitochondria; RNA stability; SLIRP; PENTATRICOPEPTIDE REPEAT PROTEINS; LEUCINE-RICH PROTEIN; DNA GENE-EXPRESSION; IN-VIVO; TRANSCRIPTION FACTOR; REGULATES TRANSLATION; POLY(A) POLYMERASE; PUNCTUATION MODEL; PPR PROTEINS; MTDNA;

D O I：

10.1038/emboj.2011.392

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Regulation of mtDNA expression is critical for maintaining cellular energy homeostasis and may, in principle, occur at many different levels. The leucine-rich pentatricopeptide repeat containing (LRPPRC) protein regulates mitochondrial mRNA stability and an amino-acid substitution of this protein causes the French-Canadian type of Leigh syndrome (LSFC), a neurodegenerative disorder characterized by complex IV deficiency. We have generated conditional Lrpprc knockout mice and show here that the gene is essential for embryonic development. Tissue-specific disruption of Lrpprc in heart causes mitochondrial cardiomyopathy with drastic reduction in steady-state levels of most mitochondrial mRNAs. LRPPRC forms an RNA-dependent protein complex that is necessary for maintaining a pool of non-translated mRNAs in mammalian mitochondria. Loss of LRPPRC does not only decrease mRNA stability, but also leads to loss of mRNA polyadenylation and the appearance of aberrant mitochondrial translation. The translation pattern without the presence of LRPPRC is misregulated with excessive translation of some transcripts and no translation of others. Our findings point to the existence of an elaborate machinery that regulates mammalian mtDNA expression at the post-transcriptional level. The EMBO Journal (2012) 31, 443-456. doi:10.1038/emboj.2011.392; Published online 1 November 2011

引用

页码：443 / 456

页数：14

共 60 条

[1] Pentatricopeptide Repeat Proteins Stimulate mRNA Adenylation/Uridylation to Activate Mitochondrial Translation in Trypanosomes [J].