Determinants for binding of a 40 kDa protein to the leaders of yeast mitochondrial mRNAs

Dekker, P.; Stuurman, Jeroen; Oosterum, K. van; Grivell, Leslie A.

doi:10.1093/nar/20.11.2647

Cited by 20 publications

(35 citation statements)

References 36 publications

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“…The eighth mRNA encodes VAR1, a hydrophilic component of mitochondrial ribosomes. In the compact 5′-untranslated region of the COX2 transcript (Figure 1) (13) have suggested that binding of this soluble matrix enzyme might repress translation until an appropriate association between the mRNA and hydrophobic elements in mitochondrial membranes is attained.…”

Section: Discussionmentioning

confidence: 99%

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Allosteric Inhibition of NAD⁺-Specific Isocitrate Dehydrogenase by a Mitochondrial mRNA

2000

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NAD+-specific isocitrate dehydrogenase (IDH) has been reported to bind sequences in 5'-untranslated regions of yeast mitochondrial mRNAs. In the current study, an RNA transcript containing the 5'-untranslated region of the mRNA from the yeast mitochondrial COX2 gene is shown to be an allosteric inhibitor of the affinity-purified yeast enzyme. At 0.1 microM concentrations of the transcript, velocity of the IDH reaction is reduced to 20% of the value obtained in the absence of the RNA transcript. This inhibition is due to a 2. 5-fold increase in the S0.5 value for isocitrate. Significant inhibition of IDH activity is also obtained with a transcript containing a portion of the 5'-untranslated region of the yeast mitochondrial ATP9 gene and with an antisense form of the COX2 transcript, both of which contain potential stem-loop secondary structures implicated in binding of IDH. In contrast, much higher concentrations of yeast tRNA or poly(A)mRNA, respectively, 33- and 60-fold greater than that required for the COX2 transcript, are required to produce a 50% decrease in velocity. These results suggest that inhibition of activity is relatively specific for the 5'-untranslated regions of mitochondrial mRNAs. All measurable inhibition of IDH activity by RNA is eliminated by addition of 100 microM concentrations of the allosteric activator AMP. At equivalent concentrations, dAMP is less efficient than AMP as an allosteric activator of IDH and is proportionally less effective in protecting against inhibition of activity by the COX2 transcript. Other nucleotides that are not allosteric activators fail to protect IDH activity from inhibitory effects of RNA. Thus, alleviation of catalytic inhibition of IDH by mitochondrial mRNA correlates with the property of allosteric activation.

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Section: Discussionmentioning

confidence: 99%

“…The holoenzyme binds sequences near potentially conserved secondary structures within the 5′ untranslated regions of all eight major yeast mitochondrial mRNA transcripts (13). Both IDH subunits are necessary for this RNA binding (12).…”

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confidence: 99%

Allosteric Inhibition of NAD⁺-Specific Isocitrate Dehydrogenase by a Mitochondrial mRNA

2000

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“…Suv3 is part of the mitochondrial RNA degradosome and is also involved in mitochondrial DNA maintenance and COX1 aI5␤ intron splicing (52)(53)(54). (NAD ϩ )-dependent isocitrate dehydrogenase is known to bind in vitro to mitochondrial mRNAs and probably can modulate translation (55)(56)(57)(58). In addition to the three described roles for Pet54, it could be possible that this protein has some function in the assembly of the CcO because it has been detected in supercomplexes (59).…”

Section: Discussionmentioning

confidence: 99%

A Novel Function of Pet54 in Regulation of Cox1 Synthesis in Saccharomyces cerevisiae Mitochondria

Mayorga

Camacho‐Villasana

Shingú-Vázquez

et al. 2016

Journal of Biological Chemistry

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Cytochrome c oxidase assembly requires the synthesis of the mitochondria-encoded core subunits, Cox1, Cox2, and Cox3. In yeast, Pet54 protein is required to activate translation of the COX3 mRNA and to process the aI5␤ intron on the COX1 transcript. Here we report a third, novel function of Pet54 on Cox1 synthesis. We observed that Pet54 is necessary to achieve an efficient Cox1 synthesis. Translation of the COX1 mRNA is coupled to the assembly of cytochrome c oxidase by a mechanism that involves Mss51. This protein activates translation of the COX1 mRNA by acting on the COX1 5-UTR, and, in addition, it interacts with the newly synthesized Cox1 protein in high molecular weight complexes that include the factors Coa3 and Cox14. Deletion of Pet54 decreased Cox1 synthesis, and, in contrast to what is commonly observed for other assembly mutants, double deletion of cox14 or coa3 did not recover Cox1 synthesis. Our results show that Pet54 is a positive regulator of Cox1 synthesis that renders Mss51 competent as a translational activator of the COX1 mRNA and that this role is independent of the assembly feedback regulatory loop of Cox1 synthesis. Pet54 may play a role in Mss51 hemylation/conformational change necessary for translational activity. Moreover, Pet54 physically interacts with the COX1 mRNA, and this binding was independent of the presence of Mss51.Cytochrome c oxidase (CcO) 3 is the last electron acceptor of the mitochondrial respiratory chain. In the yeast Saccharomyces cerevisiae, this enzyme contains 12 subunits, three of which (Cox1, Cox2, and Cox3) are encoded by the mitochondrial DNA. Assembly of CcO is a complex process regulated by more than 25 factors and chaperones (for reviews, see Ref. 1). The first steps of CcO biogenesis involve the translational activation of the mitochondria-encoded mRNAs COX1, COX2, and COX3 by mRNA-specific proteins. Translational activation of the COX1 mRNA depends on Pet309 and Mss51 (2, 3), whereas COX2 translation depends on Pet111 (4, 5), and COX3 mRNA translation depends on Pet54, Pet122, and Pet494 (6 -9). These proteins act on the target mRNA 5Ј-UTRs to allow translation by the mitochondrial ribosomes. They interact with each other and with the mitochondrial inner membrane and are thought to tether translation initiation close to the assembly sites of CcO in the membrane (for a review, see Ref. 10) (11). The mitochondria-encoded Cox1, Cox2, and Cox3 subunits are proposed to assemble from three different modules, each containing a specific subset of nucleus-encoded subunits (12-14).Cox1, the largest subunit of the CcO, carries the heme aa 3 -Cu B center to reduce oxygen. Synthesis of Cox1 inside mitochondria is highly regulated. If CcO assembly is blocked by mutations on either integral subunits or accessory chaperones, Cox1 synthesis is down-regulated (15, 16). It is proposed that by this mechanism, mitochondria avoids accumulation of pro-oxidant Cox1 intermediates (17). In addition to its role as translational activator of COX1 mRNA, Mss51 also physically inter...

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“…For isocitrate dehydrogenase, however, it is as yet unclear why two so disparate activities are combined in a single protein. It has previously been speculated that p40 may act as a translational repressor [92]. Such a role would account for the finding that chimeric mRNAs apparently lacking p40 binding sites are still translatable and goes some way towards explaining why p40 disrupted strains maintain the ability to grow (albeit slowly) on certain non-fermentable substrates [94].…”

Section: Yeast Mitochondrial Nad+-dependent Isocitrate Dehydrogenase mentioning

confidence: 99%

“…An additional protein that specifically interacts with leader sequences of all major mRNAs has been identified by a biochemical approach [91,92]. This 40 kDa protein (p40) is nuclear encoded, exclusively present in mitochondria and highly abundant [93].…”

Section: Yeast Mitochondrial Nad+-dependent Isocitrate Dehydrogenase mentioning

confidence: 99%

Protein synthesis in mitochondria

Pel

Grivell

1994

Mol Biol Rep

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Determinants for binding of a 40 kDa protein to the leaders of yeast mitochondrial mRNAs

Cited by 20 publications

References 36 publications

Allosteric Inhibition of NAD⁺-Specific Isocitrate Dehydrogenase by a Mitochondrial mRNA

Allosteric Inhibition of NAD⁺-Specific Isocitrate Dehydrogenase by a Mitochondrial mRNA

A Novel Function of Pet54 in Regulation of Cox1 Synthesis in Saccharomyces cerevisiae Mitochondria

Protein synthesis in mitochondria

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Determinants for binding of a 40 kDa protein to the leaders of yeast mitochondrial mRNAs

Cited by 20 publications

References 36 publications

Allosteric Inhibition of NAD+-Specific Isocitrate Dehydrogenase by a Mitochondrial mRNA

Allosteric Inhibition of NAD+-Specific Isocitrate Dehydrogenase by a Mitochondrial mRNA

A Novel Function of Pet54 in Regulation of Cox1 Synthesis in Saccharomyces cerevisiae Mitochondria

Protein synthesis in mitochondria

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Allosteric Inhibition of NAD⁺-Specific Isocitrate Dehydrogenase by a Mitochondrial mRNA

Allosteric Inhibition of NAD⁺-Specific Isocitrate Dehydrogenase by a Mitochondrial mRNA