Rmd9p controls the processing/stability of mitochondrial mRNAs and its overexpression compensates for a partial deficiency of oxa1p in Saccharomyces cerevisiae.
[en] Oxa1p is a key component of the general membrane insertion machinery of eukaryotic respiratory complex subunits encoded by the mitochondrial genome. In this study, we have generated a respiratory-deficient mutant, oxa1-E65G-F229S, that contains two substitutions in the predicted intermembrane space domain of Oxa1p. The respiratory deficiency due to this mutation is compensated for by overexpressing RMD9. We show that Rmd9p is an extrinsic membrane protein facing the matrix side of the mitochondrial inner membrane. Its deletion leads to a pleiotropic effect on respiratory complex biogenesis. The steady-state level of all the mitochondrial mRNAs encoding respiratory complex subunits is strongly reduced in the Deltarmd9 mutant, and there is a slight decrease in the accumulation of two RNAs encoding components of the small subunit of the mitochondrial ribosome. Overexpressing RMD9 leads to an increase in the steady-state level of mitochondrial RNAs, and we discuss how this increase could suppress the oxa1 mutations and compensate for the membrane insertion defect of the subunits encoded by these mRNAs.
Disciplines :
Biochemistry, biophysics & molecular biology
Author, co-author :
Nouet, Cécile ; Université de Liège - ULiège > Département des sciences de la vie > Génomique fonctionnelle et imagerie moléculaire végétale
Bourens, Myriam
Hlavacek, Otakar
Marsy, Sophie
Lemaire, Claire
Dujardin, Genevieve
Language :
English
Title :
Rmd9p controls the processing/stability of mitochondrial mRNAs and its overexpression compensates for a partial deficiency of oxa1p in Saccharomyces cerevisiae.
Publication date :
2007
Journal title :
Genetics
ISSN :
0016-6731
eISSN :
1943-2631
Publisher :
Genetics Society of America, Baltimore, United States - Maryland
ALTAMURA, N., N. CAPITANIO, N. BONNEFOY, S. PAPA and G. DUJARDIN, 1996 The Saccharomyces cerevisiae OXA1 gene is required for the correct assembly of cytochrome c oxidase and oligomycin-sensitive ATP synthase. FEBS Lett. 382: 111-115.
AMIOTT, E., and J. JAEHNING, 2006 Mitochondrial transcription is regulated via an ATP sensing mechanism that couples RNA abundance to respiration. Mol. Cell 22: 329-338.
BARRIENTOS, A., M. H. BARROS, I. VALNOT, A. ROTIG, P. RUSTIN et al., 2002 Cytochrome oxidase in health and disease. Gene 286: 53-63.
BARRIENTOS, A., A. ZAMBRANO and A. TZAGOLOFF, 2004 Mss51p and Cox14p jointly regulate mitochondrial Cox1p expression in Saccharomyces cerevisiae. EMBO J. 23: 3472-3482.
BAUER, M., M. BEHRENS, K. ESSER, G. MICHAELIS and E. PRATJE, 1994 PET1402, a nuclear gene required for proteolytic processing of cytochrome oxidase subunit 2 in yeast. Mol. Gen. Genet. 245: 272-278.
BONNEAUD, N., O. OZIER-KALOGEROPOULOS, G. Y. LI, M. LABOUESSE, L. MINVIELLE-SEBASTIA et al., 1991 A family of low and high copy replicative, integrative and single-stranded S. cerevisiae/E. coli shuttle vectors. Yeast 7: 609-615.
BONNEFOY, N., F. CHALVET, P. HAMEL, P. P. SLONIMSKI and G. DUJARDIN, 1994 OXA1, a Saccharomyces cerevisiae nuclear gene, whose sequence is conserved in prokaryotes and eukaryotes, controls cytochrome c oxidase biogenesis. J. Mol. Biol. 239: 201-212.
CAMOUGRAND, N., P. PELISSIER, J. VELOURS and M. GUERIN, 1995 NCA2, a second nuclear gene required for the control of mitochondrial synthesis of subunit 6 and 8 in S. cerevisiae. J. Mol. Biol. 247: 588-596.
CELEBI, N., L. YI, S. J. FACEY, A. KUHN and R. E. DALBEY, 2006 Membrane biogenesis of subunit II of cytochrome bo oxidase: contrasting requirements for insertion of N-terminal and C-terminal domains. J. Mol. Biol. 357: 1428-1436.
CHEN, W., M. A. ISLAS-OSUNA and C. L. DIECKMANN, 1999 Suppressor analysis of mutations in the 59-untranslated region of COB mRNA identifies components of general pathways for mitochondrial mRNA processing and decay in Saccharomyces cerevisiae. Genetics 151: 1315-1325.
CONTAMINE, V., and M. PICARD, 2000 Maintenance and integrity of the mitochondrial genome: a plethora of nuclear genes in the budding yeast. Microbiol. Mol. Biol. Rev. 64: 281-315.
COSTANZO, M. C., N. BONNEFOY, E. H. WILLIAMS, G. D. CLARK-WALKER and T. D. FOX, 2000 Highly diverged homologs of Saccharomyces cerevisiae mitochondrial mRNA-specific translational activators have orthologous functions in other budding yeasts. Genetics 154: 999-1012.
DALBEY, R. E., and A. KUHN, 2004 YidC family members are involved in the membrane insertion, lateral integration, folding, and assembly of membrane proteins. J. Cell Biol. 166: 769-774.
DIECKMANN, C. L., L. K. PAPE and A. TZAGOLOFF, 1982 Identification and cloning of a yeast nuclear gene (CBP1) involved in expression of mitochondrial cytochrome b. Proc. Natl. Acad. Sci. USA 79: 1805-1809.
DIMMER, K. S., S. FRITZ, F. FUCHS, M. MESSERSCHMITT, N. WEINBACH et al., 2002 Genetic basis of mitochondrial function and morphology in Saccharomyces cerevisiae. Mol. Biol. Cell 13: 847-853.
DUJARDIN, G., P. PAJOT, O. GROUDINSKY and P. P. SLONIMSKI, 1980 Long range control circuits within mitochondria and between nucleus and mitochondria. I. Methodology and phenomenology of suppressors. Mol. Gen. Genet. 179: 469-482.
DZIEMBOWSKI, A., J. PIWOWARSKI, R. HOSER, M. MINCZUK, A. DMOCHOWSKA et al., 2003 The yeast mitochondrial degradosome. Its composition, interplay between RNA helicase and RNase activities and the role in mitochondrial RNA metabolism. J. Biol. Chem. 278: 1603-1611.
ELLIS, T. P., K. G. HELFENBEIN, A. TZAGOLOFF and C. L. DIECKMANN, 2004 Aep3p stabilizes the mitochondrial bicistronic mRNA encoding subunits 6 and 8 of the H+-translocating ATP synthase of Saccharomyces cerevisiae. J. Biol. Chem. 279: 15728-15733.
ELLIS, T. P., M. S. SCHONAUER and C. L. DIECKMANN, 2005 CBT1 interacts genetically with CBP1 and the mitochondrially encoded cytochrome b gene and is required to stabilize the mature cytochrome b mRNA of Saccharomyces cerevisiae. Genetics 171: 949-957.
ENYENIHI, A. H., and W. S. SAUNDERS, 2003 Large-scale functional genomic analysis of sporulation and meiosis in Saccharomyces cerevisiae. Genetics 163: 47-54.
FALQUET, L., M. PAGNI, P. BUCHER, N. HULO, C. J. SIGRIST et al., 2002 The PROSITE database: its status in 2002. Nucleic Acids Res. 30: 235-238.
FIORI, A., T. L. MASON and T. D. FOX, 2003 Evidence that synthesis of the Saccharomyces cerevisiae mitochondrially encoded ribosomal protein Var1p may be membrane localized. Eukaryot. Cell 2: 651-653.
FOX, T. D., 1996 Translational control of endogenous and recoded nuclear genes in yeast mitochondria: regulation and membrane targeting. Experientia 52: 1130-1135.
GREEN-WILLMS, N. S., T. D. FOX and M. C. COSTANZO, 1998 Functional interactions between yeast mitochondrial ribosomes and mRNA 5′ untranslated leaders. Mol. Cell. Biol. 18: 1826-1834.
GRIVELL, L. A., M. ARTAL-SANZ, G. HAKKAART, L. DE JONG, L. G. NIJTMANS et al., 1999 Mitochondrial assembly in yeast. FEBS Lett. 452: 57-60.
GROUDINSKY, O., I. BOUSQUET, M. G. WALLIS, P. P. SLONIMSKI and G. DUJARDIN, 1993 The NAM1/MTF2 nuclear gene product is selectively required for the stability and/or processing of mitochondrial transcripts of the atp6 and of the mosaic, cox1 and cytb genes in Saccharomyces cerevisiae. Mol. Gen. Genet. 240: 419-427.
HAFFTER, P., and T. D. FOX, 1992 Suppression of carboxy-terminal truncations of the yeast mitochondrial mRNA-specific translational activator PET122 by mutations in two new genes, MRP17 and PET127. Mol. Gen. Genet. 235: 64-73.
HAMEL, P., C. LEMAIRE, N. BONNEFOY, P. BRIVET-CHEVILLOTTE and G. DUJARDIN, 1998 Mutations in the membrane anchor of yeast cytochrome c1 compensate for the absence of Oxa1p and generate carbonate-extractable forms of cytochrome c1. Genetics 150: 601-611.
HE, S., and T. D. FOX, 1997 Membrane translocation of mitochondrially coded Cox2p: distinct requirements for export of N and C termini and dependence on the conserved protein Oxa1p. Mol. Biol. Cell 8: 1449-1460.
HELL, K., J. M. HERRMANN, E. PRATJE, W. NEUPERT and R. A. STUART, 1998 Oxa1p, an essential component of the N-tail protein export machinery in mitochondria. Proc. Natl. Acad. Sci. USA 95: 2250-2255.
HELL, K., W. NEUPERT and R. A. STUART, 2001 Oxa1p acts as a general membrane insertion machinery for proteins encoded by mitochondrial DNA. EMBO J. 20: 1281-1288.
HERRMANN, J. M., and N. BONNEFOY, 2004 Protein export across the inner membrane of mitochondria: the nature of translocated domains determines the dependence on the Oxa1 translocase. J. Biol. Chem. 279: 2507-2512.
HERRMANN, J. M., and S. FUNES, 2005 Biogenesis of cytochrome oxidase-sophisticated assembly lines in the mitochondrial inner membrane. Gene 354: 43-52.
HERRMANN, J. M., W. NEUPERT and R. A. STUART, 1997 Insertion into the mitochondrial inner membrane of a polytopic protein, the nuclear-encoded Oxa1p. EMBO J. 16: 2217-2226.
HLAVACEK, O., M. BOURENS, V. SALONE, N. LACHACINSKI, C. LEMAIRE et al., 2005 The transcriptional activator HAP4 is a high copy suppressor of an oxa1 yeast mutation. Gene 354: 53-57.
HUH, W. K., J. V. FALVO, L. C. GERKE, A. S. CARROLL, R. W. HOWSON et al., 2003 Global analysis of protein localization in budding yeast. Nature 425: 686-691.
ISLAS-OSUNA, M. A., T. P. ELLIS, L. L. MARNELL, T. M. MITTELMEIER and C. L. DIECKMANN, 2002 Cbp1 is required for translation of the mitochondrial cytochrome b mRNA of Saccharomyces cerevisiae. J. Biol. Chem. 277: 37987-37990.
JIA, L., M. DIENHART, M. SCHRAMP, M. MCCAULEY, K. HELL et al., 2003 Yeast Oxa1 interacts with mitochondrial ribosomes: the importance of the C-terminal region of Oxa1. EMBO J. 22: 6438-6447.
KERMORGANT, M., N. BONNEFOY and G. DUJARDIN, 1997 Oxa1p, which is required for cytochrome c oxidase and ATP synthase complex formation, is embedded in the mitochondrial inner membrane. Curr. Genet. 31: 302-307.
KHALIMONCHUK, O., and G. RODEL, 2005 Biogenesis of cytochrome c oxidase. Mitochondrion 5: 363-388.
KRAUSE, K., R. LOPES DE SOUZA, D. G. ROBERTS and C. L. DIECKMANN, 2004 The mitochondrial message-specific mRNA protectors Cbp1 and Pet309 are associated in a high-molecular weight complex. Mol. Biol. Cell 15: 2674-2683.
KRAUSE-BUCHHOLZ, U., K. SCHOBEL, S. LAUFFER and G. RODEL, 2005 Saccharomyces cerevisiae translational activator Cbs1p is associated with translationally active mitochondrial ribosomes. Biol. Chem. 386: 407-415.
LEMAIRE, C., P. HAMEL, J. VELOURS and G. DUJARDIN, 2000 Absence of the mitochondrial AAA protease Yme1p restores F0-ATPase subunit accumulation in an oxa1 deletion mutant of Saccharomyces cerevisiae. J. Biol. Chem. 275: 23471-23475.
LEMAIRE, C., F. GUIBET-GRANDMOUGIN, D. ANGLES, G. DUJARDIN and N. BONNEFOY, 2004 A yeast mitochondrial membrane methyltransferase-like protein can compensate for oxa1 mutations. J. Biol. Chem. 279: 47464-47472.
LONGTINE, M. S., A. MCKENZIE, III, D. J. DEMARINI, N. G. SHAH, A. WACH et al., 1998 Additional modules for versatile and economical PCR-based gene deletion and modification in Saccharomyces cerevisiae. Yeast 14: 953-961.
LURIN, C., C. ANDRES, S. AUBOURG, M. BELLAOUI, F. BITTON et al., 2004 Genome-wide analysis of Arabidopsis pentatricopeptide repeat proteins reveals their essential role in organelle biogenesis. Plant Cell 16: 2089-2103.
MANTHEY, G. M., and J. E. MCEWEN, 1995 The product of the nuclear gene PET309 is required for translation of mature mRNA and stability or production of intron-containing RNAs derived from the mitochondrial COX1 locus of Saccharomyces cerevisiae. EMBO J. 14: 4031-4043.
MARGEOT, A., M. GARCIA, W. WANG, E. TETAUD, J. P. DI RAGO et al., 2005 Why are many mRNAs translated to the vicinity of mitochondria: a role in protein complex assembly? Gene 354: 64-71.
MEYER, W., M. BAUER and E. PRATJE, 1997 A mutation in cytochrome oxidase subunit 2 restores respiration of the mutant pet ts1402. Curr. Genet. 31: 401-407.
MIN, J., and H. P. ZASSENHAUS, 1993 Identification of a protein complex that binds to a dodecamer sequence found at the 3′ ends of yeast mitochondrial mRNAs. Mol. Cell. Biol. 13: 4167-4173.
NAITHANI, S., S. A. SARACCO, C. A. BUTLER and T. D. FOX, 2003 Interactions among COX1, COX2, and COX3 mRNA-specific translational activator proteins on the inner surface of the mitochondrial inner membrane of Saccharomyces cerevisiae. Mol. Biol. Cell 14: 324-333.
NARGANG, F. E., M. PREUSS, W. NEUPERT and J. M. HERRMANN, 2002 The Oxa1 protein forms a homooligomeric complex and is an essential part of the mitochondrial export translocase in Neurospora crassa. J. Biol. Chem. 277: 12846-12853.
NOUWEN, N., and A. J. DRIESSEN, 2002 SecDFyajC forms a heterotetrameric complex with YidC. Mol. Microbiol. 44: 1397-1405.
OSINGA, K. A., E. DE VRIES, G. VAN DER HORST and H. F. TABAK, 1984 Processing of yeast mitochondrial messenger RNAs at a conserved dodecamer sequence. EMBO J. 3: 829-834.
OTT, M., M. PRESTELE, H. BAUERSCHMITT, S. FUNES, N. BONNEFOY et al., 2006 Mba1, a membrane-associated ribosome receptor in mitochondria. EMBO J. 25: 1603-1610.
PEREZ-MARTINEZ, X., S. A. BROADLEY and T. D. FOX, 2003 Mss51p promotes mitochondrial Cox1p synthesis and interacts with newly synthesized Cox1p. EMBO J. 22: 5951-5961.
RACKI, W. J., A. M. BECAM, F. NASR and C. J. HERBERT, 2000 Cbk1p, a protein similar to the human myotonic dystrophy kinase, is essential for normal morphogenesis in Saccharomyces cerevisiae. EMBO J. 19: 4524-4532.
RODEHEFFER, M. S., B. E. BOONE, A. C. BRYAN and G. S. SHADEL, 2001 Nam1p, a protein involved in RNA processing and translation, is coupled to transcription through an interaction with yeast mitochondrial RNA polymerase. J. Biol. Chem. 276: 8616-8622.
RODEL, G., 1997 Translational activator proteins required for cytochrome b synthesis in Saccharomyces cerevisiae. Curr. Genet. 31: 375-379.
ROGOWSKA, A. T., O. PUCHTA, A. M. CZARNECKA, A. KANIAK, P. P. STEPIEN et al., 2006 Balance between transcription and RNA degradation is vital for Saccharomyces cerevisiae mitochondria: reduced transcription rescues the phenotype of deficient RNA degradation. Mol. Biol. Cell 17: 1184-1193.
ROUILLARD, J. M., M. E. DUFOUR, B. THEUNISSEN, E. MANDART, G. DUJARDIN et al., 1996 SLS1, a new Saccharomyces cerevisiae gene involved in mitochondrial metabolism, isolated as a synthetic lethal in association with an SSM4 deletion. Mol. Gen. Genet. 252: 700-708.
SAINT-GEORGES, Y., P. HAMEL, C. LEMAIRE and G. DUJARDIN, 2001 Role of positively charged transmembrane segments in the insertion and assembly of mitochondrial inner-membrane proteins. Proc. Natl. Acad. Sci. USA 98: 13814-13819.
SAINT-GEORGES, Y., N. BONNEFOY, J. P. DI RAGO, S. CHIRON and G. DUJARDIN, 2002 A pathogenic cytochrome b mutation reveals new interactions between subunits of the mitochondrial bc1 complex. J. Biol. Chem. 277: 49397-49402.
SANCHIRICO, M. E., T. D. FOX and T. L. MASON, 1998 Accumulation of mitochondrially synthesized Saccharomyces cerevisiae Cox2p and Cox3p depends on targeting information in untranslated portions of their mRNAs. EMBO J. 17: 5796-5804.
SELLEM, C. H., C. LEMAIRE, S. LORIN, G. DUJARDIN and A. SAINSARD-CHANET, 2005 Interaction between the oxa1 and rmp1 genes modulates respiratory complex assembly and life span in Podospora anserina. Genetics 169: 1379-1389.
SERAPHIN, B., A. BOULET, M. SIMON and G. FAYE, 1987 Construction of a yeast strain devoid of mitochondrial introns and its use to screen nuclear genes involved in mitochondrial splicing. Proc. Natl. Acad. Sci. USA 84: 6810-6814.
SICKMANN, A., J. REINDERS, Y. WAGNER, C. JOPPICH, R. ZAHEDI et al., 2003 The proteome of Saccharomyces cerevisiae mitochondria. Proc. Natl. Acad. Sci. USA 100: 13207-13212.
SZYRACH, G., M. OTT, N. BONNEFOY, W. NEUPERT and J. M. HERRMANN, 2003 Ribosome binding to the Oxa1 complex facilitates co-translational protein insertion in mitochondria. EMBO J. 22: 6448-6457.
TZAGOLOFF, A., and C. L. DIECKMANN, 1990 PET genes of Saccharomyces cerevisiae. Microbiol. Rev. 54: 211-225.
vAN BLOOIS, E., G. J. HAAN, J. W. DE GIER, B. OUDEGA and J. LUIRINK, 2006 Distinct requirements for translocation of the N-tail and C-tail of the Escherichia coli inner membrane protein CyoA. J. Biol. Chem. 281: 10002-10009.
VAN DER LAAN, M., M. L. URBANUS, C. M. TEN HAGEN-JONGMAN, N. NOUWEN, B. OUDEGA et al., 2003 A conserved function of YidC in the biogenesis of respiratory chain complexes. Proc. Natl. Acad. Sci. USA 100: 5801-5806.
WACH, A., A. BRACHAT, R. POHLMANN and P. PHILIPPSEN, 1994 New heterologous modules for classical or PCR-based gene disruptions in Saccharomyces cerevisiae. Yeast 10: 1793-1808.
WIESENBERGER, G., and T. D. FOX, 1997 Pet127p, a membrane-associated protein involved in stability and processing of Saccharomyces cerevisiae mitochondrial RNAs. Mol. Cell. Biol. 17: 2816-2824.
WILLIAMS, E. H., C. A. BUTLER, N. BONNEFOY and T. D. FOX, 2007 Translation initiation in Saccharomyces cerevisiae mitochondria: functional interactions among mitochondrial ribosomal protein Rsm28p, initiation factor 2, methionyl-tRNA formyltransferase, and novel protein Rmd9p. Genetics 175: 1117-1126.
WINZELER, E. A., D. D. SHOEMAKER, A. ASTROMOFF, H. LIANG, K. ANDERSON et al., 1999 Functional characterization of the S. cerevisiae genome by gene deletion and parallel analysis. Science 285: 901-906.
