Pentamidine inhibits mitochondrial intron splicing and translation in Saccharomyces cerevisiae

Yi Zhang, Achim Bell, Philip S. Perlman, Michael J Leibowitz

Research output: Contribution to journalArticle

37 Citations (Scopus)

Abstract

Pentamidine inhibits in vitro splicing of nuclear group I introns from rRNA genes of some pathogenic fungi and is known to inhibit mitochondrial function in yeast. Here we report that pentamidine inhibits the self-splicing of three group I and two group II introns of yeast mitochondria. Comparison of yeast strains with different configurations of mitochondrial introns (12, 5, 4, or 0 introns) revealed that strains with the most introns were the most sensitive to growth inhibition by pentamidine on glycerol medium. Analysis of blots of RNA from yeast strains grown in raffinose medium in the presence or absence of pentamidine revealed that the splicing of seven group I and two group II introns that have intron reading frames was inhibited by the drug to varying extents. Three introns without reading frames were unaffected by the drug in vivo, and two of these were inhibited in vitro, implying that the drug affects splicing by acting directly on RNA in vitro, but on another target in vivo. Because the most sensitive introns in vivo are the ones whose splicing depends on a maturase encoded by the intron reading frames, we tested pentamidine for effects on mitochondrial translation. We found that the drug inhibits mitochondrial but not cytoplasmic translation in cells at concentrations that inhibit mitochondrial intron splicing. Therefore, pentamidine is a potent and specific inhibitor of mitochondrial translation, and this effect explains most or all of its effects on respiratory growth and on in vivo splicing of mitochondrial introns.

Original languageEnglish (US)
Pages (from-to)937-951
Number of pages15
JournalRNA
Volume6
Issue number7
DOIs
StatePublished - Jul 2000
Externally publishedYes

Fingerprint

Pentamidine
Introns
Saccharomyces cerevisiae
Reading Frames
Yeasts
Pharmaceutical Preparations
RNA
Raffinose
Growth
rRNA Genes
Glycerol
Mitochondria

Keywords

  • Intron splicing
  • Mitochondria
  • Pentamidine
  • Translation
  • Yeast

ASJC Scopus subject areas

  • Genetics
  • Molecular Biology

Cite this

Pentamidine inhibits mitochondrial intron splicing and translation in Saccharomyces cerevisiae. / Zhang, Yi; Bell, Achim; Perlman, Philip S.; Leibowitz, Michael J.

In: RNA, Vol. 6, No. 7, 07.2000, p. 937-951.

Research output: Contribution to journalArticle

Zhang, Yi ; Bell, Achim ; Perlman, Philip S. ; Leibowitz, Michael J. / Pentamidine inhibits mitochondrial intron splicing and translation in Saccharomyces cerevisiae. In: RNA. 2000 ; Vol. 6, No. 7. pp. 937-951.
@article{e9c5d7d38cf941b1b20d550ef7ccb5c1,
title = "Pentamidine inhibits mitochondrial intron splicing and translation in Saccharomyces cerevisiae",
abstract = "Pentamidine inhibits in vitro splicing of nuclear group I introns from rRNA genes of some pathogenic fungi and is known to inhibit mitochondrial function in yeast. Here we report that pentamidine inhibits the self-splicing of three group I and two group II introns of yeast mitochondria. Comparison of yeast strains with different configurations of mitochondrial introns (12, 5, 4, or 0 introns) revealed that strains with the most introns were the most sensitive to growth inhibition by pentamidine on glycerol medium. Analysis of blots of RNA from yeast strains grown in raffinose medium in the presence or absence of pentamidine revealed that the splicing of seven group I and two group II introns that have intron reading frames was inhibited by the drug to varying extents. Three introns without reading frames were unaffected by the drug in vivo, and two of these were inhibited in vitro, implying that the drug affects splicing by acting directly on RNA in vitro, but on another target in vivo. Because the most sensitive introns in vivo are the ones whose splicing depends on a maturase encoded by the intron reading frames, we tested pentamidine for effects on mitochondrial translation. We found that the drug inhibits mitochondrial but not cytoplasmic translation in cells at concentrations that inhibit mitochondrial intron splicing. Therefore, pentamidine is a potent and specific inhibitor of mitochondrial translation, and this effect explains most or all of its effects on respiratory growth and on in vivo splicing of mitochondrial introns.",
keywords = "Intron splicing, Mitochondria, Pentamidine, Translation, Yeast",
author = "Yi Zhang and Achim Bell and Perlman, {Philip S.} and Leibowitz, {Michael J}",
year = "2000",
month = "7",
doi = "10.1017/S1355838200991726",
language = "English (US)",
volume = "6",
pages = "937--951",
journal = "RNA",
issn = "1355-8382",
publisher = "Cold Spring Harbor Laboratory Press",
number = "7",

}

TY - JOUR

T1 - Pentamidine inhibits mitochondrial intron splicing and translation in Saccharomyces cerevisiae

AU - Zhang, Yi

AU - Bell, Achim

AU - Perlman, Philip S.

AU - Leibowitz, Michael J

PY - 2000/7

Y1 - 2000/7

N2 - Pentamidine inhibits in vitro splicing of nuclear group I introns from rRNA genes of some pathogenic fungi and is known to inhibit mitochondrial function in yeast. Here we report that pentamidine inhibits the self-splicing of three group I and two group II introns of yeast mitochondria. Comparison of yeast strains with different configurations of mitochondrial introns (12, 5, 4, or 0 introns) revealed that strains with the most introns were the most sensitive to growth inhibition by pentamidine on glycerol medium. Analysis of blots of RNA from yeast strains grown in raffinose medium in the presence or absence of pentamidine revealed that the splicing of seven group I and two group II introns that have intron reading frames was inhibited by the drug to varying extents. Three introns without reading frames were unaffected by the drug in vivo, and two of these were inhibited in vitro, implying that the drug affects splicing by acting directly on RNA in vitro, but on another target in vivo. Because the most sensitive introns in vivo are the ones whose splicing depends on a maturase encoded by the intron reading frames, we tested pentamidine for effects on mitochondrial translation. We found that the drug inhibits mitochondrial but not cytoplasmic translation in cells at concentrations that inhibit mitochondrial intron splicing. Therefore, pentamidine is a potent and specific inhibitor of mitochondrial translation, and this effect explains most or all of its effects on respiratory growth and on in vivo splicing of mitochondrial introns.

AB - Pentamidine inhibits in vitro splicing of nuclear group I introns from rRNA genes of some pathogenic fungi and is known to inhibit mitochondrial function in yeast. Here we report that pentamidine inhibits the self-splicing of three group I and two group II introns of yeast mitochondria. Comparison of yeast strains with different configurations of mitochondrial introns (12, 5, 4, or 0 introns) revealed that strains with the most introns were the most sensitive to growth inhibition by pentamidine on glycerol medium. Analysis of blots of RNA from yeast strains grown in raffinose medium in the presence or absence of pentamidine revealed that the splicing of seven group I and two group II introns that have intron reading frames was inhibited by the drug to varying extents. Three introns without reading frames were unaffected by the drug in vivo, and two of these were inhibited in vitro, implying that the drug affects splicing by acting directly on RNA in vitro, but on another target in vivo. Because the most sensitive introns in vivo are the ones whose splicing depends on a maturase encoded by the intron reading frames, we tested pentamidine for effects on mitochondrial translation. We found that the drug inhibits mitochondrial but not cytoplasmic translation in cells at concentrations that inhibit mitochondrial intron splicing. Therefore, pentamidine is a potent and specific inhibitor of mitochondrial translation, and this effect explains most or all of its effects on respiratory growth and on in vivo splicing of mitochondrial introns.

KW - Intron splicing

KW - Mitochondria

KW - Pentamidine

KW - Translation

KW - Yeast

UR - http://www.scopus.com/inward/record.url?scp=0033913732&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0033913732&partnerID=8YFLogxK

U2 - 10.1017/S1355838200991726

DO - 10.1017/S1355838200991726

M3 - Article

VL - 6

SP - 937

EP - 951

JO - RNA

JF - RNA

SN - 1355-8382

IS - 7

ER -