Characterization and tRNA Recognition of Mammalian Mitochondrial Seryl-tRNA Synthetase

Yokogawa, Takashi; Shimada, Nobukazu; Takeuchi, Naonobu; Benkowski, Lisa A.; Suzuki, Tsutomu; Omori, Akira; Ueda, Takuya; Nishikawa, Kazuya; Spremulli, Linda L.; Watanabe, Kimitsuna

doi:10.1074/jbc.m908473199

Cited by 46 publications

(42 citation statements)

References 46 publications

(42 reference statements)

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“…Ser instead of the missing extra arm, because the catalytic core in the C-terminal region is well conserved in mt SerRS (18). Despite low homology in the N-terminal domain between mt SerRS and prokaryotic enzymes, a single, long helical arm was clearly predicted in the N-terminal region of bovine mt SerRS both by the CD spectrum of the recombinant enzyme and computational analysis of the helical structure using the COILS algorithm.…”

Section: Discussionmentioning

confidence: 97%

“…In addition, each possesses an unusual secondary structure; tRNA GCU Ser (for codon AGY) lacks the entire D arm (16), whereas tRNA UGA Ser (for codon UCN) has an unusual cloverleaf configuration with an extended anticodon stem (17). We previously demonstrated that the single mt SerRS recognizes these distinct isoacceptors with almost the same activity (18). Additionally, inspection of the primary sequences of several mt SerRSs revealed differences between mammalian mt SerRS and its prokaryotic counterpart in the N-terminal domain responsible for tRNA recognition, which are in line with structural and recognition differences between the extra arms of mammalian mt and prokaryotic tRNAs Ser .…”

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confidence: 99%

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Dual Mode Recognition of Two Isoacceptor tRNAs by Mammalian Mitochondrial Seryl-tRNA Synthetase

Shimada¹,

Suzuki²,

Watanabe³

2001

Journal of Biological Chemistry

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Animal mitochondrial translation systems contain two serine tRNAs, corresponding to the codons AGY (Y ‫؍‬ U and C) and UCN (N ‫؍‬ U, C, A, and G), each possessing an unusual secondary structure; tRNA GCU Ser (for AGY) lacks the entire D arm, whereas tRNA UGA Ser (for UCN) has an unusual cloverleaf configuration. We previously demonstrated that a single bovine mitochondrial seryltRNA synthetase (mt SerRS) recognizes these topologically distinct isoacceptors having no common sequence or structure. Recombinant mt SerRS clearly footprinted at the T⌿C loop of each isoacceptor, and kinetic studies revealed that mt SerRS specifically recognized the T⌿C loop sequence in each isoacceptor. However, in the case of tRNA UGA Ser , T⌿C loop-D loop interaction was further required for recognition, suggesting that mt SerRS recognizes the two substrates by distinct mechanisms. mt SerRS could slightly but significantly misacylate mitochondrial tRNA Gln , which has the same T⌿C loop sequence as tRNA UGA Ser , implying that the fidelity of mitochondrial translation is maintained by kinetic discrimination of tRNAs in the network of aminoacyltRNA synthetases.

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Section: Discussionmentioning

confidence: 97%

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confidence: 99%

Dual Mode Recognition of Two Isoacceptor tRNAs by Mammalian Mitochondrial Seryl-tRNA Synthetase

Shimada¹,

Suzuki²,

Watanabe³

2001

Journal of Biological Chemistry

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“…It has been suggested that mutations in the S12mt gene result in translational misreading and mitochondrial dysfunction. Recently, we found that the mitochondrial seryl-tRNA synthetase (mt SerRS) gene was located upstream and adjacent to the S12mt gene (57). The genes for S12mt and mt SerRS are considered to be possible candidates for DFNA4.…”

Section: Fig 4-continuedmentioning

confidence: 99%

Proteomic Analysis of the Mammalian Mitochondrial Ribosome

Suzuki¹,

Terasaki²,

Takemoto-Hori³

et al. 2001

Journal of Biological Chemistry

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137

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The mammalian mitochondrial ribosome (mitoribosome) has a highly protein-rich composition with a small sedimentation coefficient of 55 S, consisting of 39 S large and 28 S small subunits. In the previous study, we analyzed 39 S large subunit proteins from bovine mitoribosome (Suzuki, T., Terasaki, M., Takemoto-Hori, C., Hanada, T., Ueda, T., Wada, A., and Watanabe, K. (2001) J. Biol. Chem. 276, 21724-21736). The results suggested structural compensation for the rRNA deficit through proteins of increased molecular mass in the mitoribosome. We report here the identification of 28 S small subunit proteins. Each protein was separated by radical-free high-reducing two-dimensional polyacrylamide gel electrophoresis and analyzed by liquid chromatography/mass spectrometry/mass spectrometry using electrospray ionization/ion trap mass spectrometer to identify cDNA sequence by expressed sequence tag data base searches in silico. Twenty one proteins from the small subunit were identified, including 11 new proteins along with their complete cDNA sequences from human and mouse. In addition to these proteins, three new proteins were also identified in the 55 S mitoribosome. We have clearly identified a mitochondrial homologue of S12, which is a key regulatory protein of translation fidelity and a candidate for the autosomal dominant deafness gene, DFNA4. The apoptosis-related protein DAP3 was found to be a component of the small subunit, indicating a new function for the mitoribosome in programmed cell death. In summary, we have mapped a total of 55 proteins from the 55 S mitoribosome on the two-dimensional polyacrylamide gels.

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“…Two tRNA genes that share these characteristics are the isoaccepting leucine tRNA (L CUN , L UUR ) genes. Although these tRNAs have different mRNA codon selectivities (L CUN with anticodon UAG recognizes four codons, CUA, CUG, CUC, and CUU, within mRNA transcripts; L UUR with anticodon UAA recognizes two codons, UUA and UUG), both genes code for tRNAs that accept the same amino acid and both are likely recognized by the same aminoacyl-tRNA synthetase, as shown for isoaccepting serine tRNAs within animal mtDNA (6). Likewise, the identity of these tRNA genes can be switched through a single point mutation in the third base of the anticodon triplet (e.g., TAA to TAG).…”

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Changing identities: tRNA duplication and remolding within animal mitochondrial genomes

Rawlings

Collins

Bieler

2003

Proc. Natl. Acad. Sci. U.S.A.

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Although the majority of metazoan mitochondrial genomes (mtDNAs) contain the same 37 genes, including 22 encoding transfer RNAs (tRNAs), the recognition of orthologs is not always straightforward. Here we demonstrate that inferring tRNA orthologs among taxa by using anticodon triplets and deduced secondary structure can be misleading: through a process of tRNA duplication and mutation in the anticodon triplet, remolded leucine (L UUR) tRNA genes have repeatedly taken over the role of isoaccepting LCUN leucine tRNAs within metazoan mtDNA. In the present work, data from within the gastropods and a broad survey of metazoan mtDNA suggest that tRNA leucine duplication and remolding events have occurred independently at least seven times within three major animal lineages. In all cases where the mechanism of gene remolding can be inferred with confidence, the direction is the same: from L UUR to LCUN. Gene remolding and its apparent asymmetry have significant implications for the use of mitochondrial tRNA gene orders as phylogenetic markers. Remolding complicates the identification of orthologs and can result in convergence in gene order. Careful sequence-based analysis of tRNAs can help to recognize this homoplasy, improving geneorder-based phylogenetic hypotheses and underscoring the importance of careful homology assessment. tRNA remolding also provides an additional mechanism by which gene order changes can occur within mtDNA: through the changing identity of tRNA genes themselves. Recognition of these remolding events can lead to new interpretations of gene order changes, as well as the discovery of phylogenetically relevant gene dynamics that are hidden at the level of gene order alone. Mitochondrial gene order data are being used with increasing frequency as robust molecular characters in deep-level metazoan phylogenetic studies. A fundamental assumption of molecular systematics is that orthologous genes can be recognized unambiguously. The facts that most animal mtDNAs described to date are composed of 37 genes (22 tRNAs, 2 rRNAs, and 13 protein subunits), that these genes play roles essential for oxidative metabolism, and that putative homologs have been identified in the mtDNAs of other eukaryotes (1, 2) suggest that identifying orthologs among metazoan lineages should not be problematic. In practice, however, establishing homology between mtDNA genes of distantly related organisms can be difficult at the nucleotide level because of high rates of sequence evolution. This difficulty in identifying homologs is particularly acute for short (Ϸ70-80 bp) tRNA genes. Typically, the anticodon and features of secondary structure are used to establish tRNA identity, but these can be misleading. Some tRNA genes may, through a process of duplication and point mutation(s) in the anticodon triplet, assume the identity of other tRNAs within mtDNA (3). The potential for gene remolding has been corroborated by in vitro tRNA gene knockout experiments in prokaryotic systems (4), and in studies of human mitochondrial-based dise...

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Characterization and tRNA Recognition of Mammalian Mitochondrial Seryl-tRNA Synthetase

Cited by 46 publications

References 46 publications

Dual Mode Recognition of Two Isoacceptor tRNAs by Mammalian Mitochondrial Seryl-tRNA Synthetase

Dual Mode Recognition of Two Isoacceptor tRNAs by Mammalian Mitochondrial Seryl-tRNA Synthetase

Proteomic Analysis of the Mammalian Mitochondrial Ribosome

Changing identities: tRNA duplication and remolding within animal mitochondrial genomes

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