Increased mitochondrial processing intermediates associated with three tRNALeu(UUR) gene mutations

被引：21

作者：

Koga, A ^{[1
]}

Koga, Y ^{[1
]}

Akita, Y ^{[1
]}

Fukiyama, R ^{[1
]}

Ueki, I ^{[1
]}

Yatsuga, S ^{[1
]}

Matsuishi, T ^{[1
]}

机构：

[1] Kurume Univ, Sch Med, Dept Pediat & Child Hlth, Fukuoka 8300011, Japan

来源：

NEUROMUSCULAR DISORDERS | 2003年 / 13卷 / 03期

关键词：

mitochondrial DNA mutation; RNA; dominant-negative effect;

D O I：

10.1016/S0960-8966(02)00267-5

中图分类号：

R74 [神经病学与精神病学];

学科分类号：

摘要：

Accumulation of RNA 19 has been associated with mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes. We analyzed total RNA in muscle specimens from six patients who had one of three pathogenetic point mutations in the mitochondrial tRNA(Leu(UUR)) gene, including A3243G, T3271C, and T3303C. Mitochondrial processing intermediates were identified and quantitated by Northern blotting. The percentage of DNA with the mutation also was determined in each patient. The intermediate (RNA 19) was significantly increased in all patients. The proportion of mutation-carrying RNA in processing intermediates was always higher than in the DNA fraction, suggesting that these mutations may have dominant-negative effects on mitochondrial RNA processing events at the tRNA(Leu(UUR)) gene boundary. (C) 2002 Elsevier Science B.V. All rights reserved.

引用

页码：259 / 262

页数：4

共 10 条

[1]

BINDOFF LA, 1993, J BIOL CHEM, V268, P19559

[2] Functional and molecular mitochondrial abnormalities associated with a C->T transition at position 3256 of the human mitochondrial genome - The effects of a pathogenic mitochondrial tRNA point mutation in organelle translation and RNA processing [J].

Hao, HL ;

Moraes, CT .

JOURNAL OF BIOLOGICAL CHEMISTRY, 1996, 271 (04) :2347-2352

[3]

Iwanaga R, 2001, ACTA NEUROPATHOL, V101, P179

[4] Mitochondrial DNA and RNA processing in MELAS [J].

Kaufmann, P ;

Koga, Y ;

Shanske, S ;

Hirano, M ;

DiMauro, S ;

King, MP ;

Schon, EA .

ANNALS OF NEUROLOGY, 1996, 40 (02) :172-180

[5] DEFECTS IN MITOCHONDRIAL PROTEIN-SYNTHESIS AND RESPIRATORY-CHAIN ACTIVITY SEGREGATE WITH THE TRANSFER RNA(LEU)(UUR) MUTATION ASSOCIATED WITH MITOCHONDRIAL MYOPATHY, ENCEPHALOPATHY, LACTIC-ACIDOSIS, AND STROKE-LIKE EPISODES [J].

KING, MP ;

KOGA, Y ;

DAVIDSON, M ;

SCHON, EA .

MOLECULAR AND CELLULAR BIOLOGY, 1992, 12 (02) :480-490

[6] Single-fiber analysis of mitochondrial A3243G mutation in four different phenotypes [J].

Koga, Y ;

Koga, A ;

Iwanaga, R ;

Akita, Y ;

Tubone, J ;

Matsuishi, T ;

Takane, N ;

Sato, Y ;

Kato, H .

ACTA NEUROPATHOLOGICA, 2000, 99 (02) :186-190

[7]

KOGA Y, 1995, MUSCLE NERVE, pS119

[8] MELAS exhibits dominant negative effects on mitochondrial RNA processing [J].

Koge, Y ;

Yoshino, M ;

Kato, H .

ANNALS OF NEUROLOGY, 1998, 43 (06) :835-835

[9] Impairment of tRNA processing by point mutations in mitochondrial tRNALeu(UUR) associated with mitochondrial diseases [J].

Rossmanith, W ;

Karwan, RM .

FEBS LETTERS, 1998, 433 (03) :269-274

[10] THE MITOCHONDRIAL TRANSFER RNALEU(UUR) MUTATION IN MELAS - A MODEL FOR PATHOGENESIS [J].

SCHON, EA ;

KOGA, Y ;

DAVIDSON, M ;

MORAES, CT ;

KING, MP .

BIOCHIMICA ET BIOPHYSICA ACTA, 1992, 1101 (02) :206-209

← 1 →