Methylation of 12S rRNA Is Necessary for In Vivo Stability of the Small Subunit of the Mammalian Mitochondrial Ribosome

被引：250

作者：

Metodiev, Metodi D. ^{[1
,3
]}

Lesko, Nicole ^{[1
]}

Park, Chan Bae ^{[2
]}

Camara, Yolanda ^{[1
]}

Shi, Yonghong ^{[1
]}

Wibom, Rolf ^{[1
]}

Hultenby, Kjell ^{[1
]}

Gustafsson, Claes M. ^{[1
]}

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

机构：

[1] Karolinska Inst, Dept Lab Med, Div Metab Dis, Stockholm, Sweden

[2] Ajou Univ, Sch Med, Inst Med Sci, Suwon 443721, South Korea

[3] Max Planck Inst Biol Ageing, D-50931 Cologne, Germany

来源：

CELL METABOLISM | 2009年 / 9卷 / 04期

关键词：

TRANSCRIPTION FACTOR-B; OXIDATIVE-PHOSPHORYLATION; ESCHERICHIA-COLI; METHYLTRANSFERASE ACTIVITY; DIMETHYLASE DIM1P; 3' END; MTDNA; MICE; GENE; EMBRYOGENESIS;

D O I：

10.1016/j.cmet.2009.03.001

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

The 3' end of the rRNA of the small ribosomal subunit contains two extremely highly conserved dimethylated adenines. This modification and the responsible methyltransferases are present in all three domains of life, but its function has remained elusive. We have disrupted the mouse Tfb1m, gene encoding a mitochondrial protein homologous to bacterial dimethyltransferases and demonstrate here that loss of TFB1M is embryonic lethal. Disruption of Tfb1m in heart leads to complete loss of adenine dimethylation of the rRNA of the small mitochondrial ribosomal subunit, impaired assembly of the mitochondrial ribosome, and abolished mitochondrial translation. In addition, we present biochemical evidence that TFB1M does not activate or repress transcription in the presence of TFB2M. Our results thus show that TFB1M is a nonredundant dimethyltransferase in mammalian mitochondria. In addition, we provide a possible explanation for the universal conservation of adenine dimethylation of rRNA by showing a critical role in ribosome maintenance.

引用

页码：386 / 397

页数：12

共 37 条

[1]

COTE C, 1989, J BIOL CHEM, V264, P8487

[2] Evidence for an early gene duplication event in the evolution of the mitochondrial transcription factor B family and maintenance of rRNA methyltransferase activity in human mtTFB1 and mtTFB2 [J].

Cotney, Justin ;

Shadel, Gerald S. .

JOURNAL OF MOLECULAR EVOLUTION, 2006, 63 (05) :707-717

[3] The adenosine dimethyltransferase KsgA recognizes a specific conformational state of the 30S ribosomal subunit [J].

Desai, Pooia M. ;

Rife, Jason P. .

ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS, 2006, 449 (1-2) :57-63

[4] Mitochondrial transcription factor A regulates mtDNA copy number in mammals [J].

Ekstrand, MI ;

Falkenberg, M ;

Rantanen, A ;

Park, CB ;

Gaspari, M ;

Hultenby, K ;

Rustin, P ;

Gustafsson, CM ;

Larsson, NG .

HUMAN MOLECULAR GENETICS, 2004, 13 (09) :935-944

[5]

Enriquez J A, 1996, Methods Enzymol, V264, P50, DOI 10.1016/S0076-6879(96)64008-7

[6] Mitochondrial transcription factors B1 and B2 activate transcription of human mtDNA [J].

Falkenberg, M ;

Gaspari, M ;

Rantanen, A ;

Trifunovic, A ;

Larsson, NG ;

Gustafsson, CM .

NATURE GENETICS, 2002, 31 (03) :289-294

[7] DNA replication and transcription in mammalian mitochondria [J].

Falkenberg, Maria ;

Larsson, Nils-Goeran ;

Gustafsson, Claes M. .

ANNUAL REVIEW OF BIOCHEMISTRY, 2007, 76 :679-699

[8] Control of mitochondrial transcription specificity factors (TFB1M and TFB2M) by nuclear respiratory factors (NRF-1 and NRF-2) and PGC-1 family coactivators [J].

Gleyzer, N ;

Vercauteren, K ;

Scarpulla, RC .

MOLECULAR AND CELLULAR BIOLOGY, 2005, 25 (04) :1354-1366

[9] Mitochondrial DNA polymerase gamma is essential for mammalian embryogenesis [J].

Hance, N ;

Ekstrand, MI ;

Trifunovic, A .

HUMAN MOLECULAR GENETICS, 2005, 14 (13) :1775-1783

[10] CHANGE IN METHYLATION OF 16S RIBOSOMAL RNA ASSOCIATED WITH MUTATION TO KASUGAMYCIN RESISTANCE IN ESCHERICHIA-COLI [J].

HELSER, TL ;

DAVIES, JE ;

DAHLBERG, JE .

NATURE-NEW BIOLOGY, 1971, 233 (35) :12-&

← 1 2 3 4 →