A Novel Modified Nucleoside Found at the First Position of the Anticodon of Methionine tRNA from Bovine Liver Mitochondria

Moriya, Jiro; Yokogawa, Takashi; Wakita, Kawori; Ueda, Takuya; Nishikawa, Kazuya; Crain, Pamela F.; Hashizume, Takeshi; Pomerantz, Steven C.; McCloskey, James A.

doi:10.1021/bi00174a033

Cited by 107 publications

(86 citation statements)

References 26 publications

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“…Our findings imply that in vivo a large fraction of the m 5 C34‐containing mt‐tRNA Met is oxidised by ABH1, which is in line with previous reports that found the f 5 C34 modification in mt‐tRNA Met (Moriya et al , 1994; Takemoto et al , 2009; Suzuki & Suzuki, 2014). However, we also observed that mt‐tRNA Met carrying m 5 C34 is present in vivo , which is supported by findings of Van Haute et al (2016), and that this modification state of mt‐tRNA Met is efficiently recruited to the P site of the ribosome in vitro .…”

Section: Discussionsupporting

confidence: 93%

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NSUN 3 and ABH 1 modify the wobble position of mt‐t RNA ^Met to expand codon recognition in mitochondrial translation

et al. 2016

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Mitochondrial gene expression uses a non‐universal genetic code in mammals. Besides reading the conventional AUG codon, mitochondrial (mt‐)tRNAM et mediates incorporation of methionine on AUA and AUU codons during translation initiation and on AUA codons during elongation. We show that the RNA methyltransferase NSUN3 localises to mitochondria and interacts with mt‐tRNAM et to methylate cytosine 34 (C34) at the wobble position. NSUN3 specifically recognises the anticodon stem loop (ASL) of the tRNA, explaining why a mutation that compromises ASL basepairing leads to disease. We further identify ALKBH1/ABH1 as the dioxygenase responsible for oxidising m5C34 of mt‐tRNAM et to generate an f5C34 modification. In vitro codon recognition studies with mitochondrial translation factors reveal preferential utilisation of m5C34 mt‐tRNA Met in initiation. Depletion of either NSUN3 or ABH1 strongly affects mitochondrial translation in human cells, implying that modifications generated by both enzymes are necessary for mt‐tRNAM et function. Together, our data reveal how modifications in mt‐tRNAM et are generated by the sequential action of NSUN3 and ABH1, allowing the single mitochondrial tRNAM et to recognise the different codons encoding methionine.

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Section: Discussionsupporting

confidence: 93%

“…Previous reports suggested that mt‐tRNA Met can be modified at position 34 to contain a 5‐formylcytosine (f 5 C; Moriya et al , 1994; Suzuki & Suzuki, 2014). We hypothesised that a specific oxygenase might oxidise the m 5 C34 moiety established by NSUN3 to generate an f 5 C34 modification in mt‐tRNA Met .…”

Section: Resultsmentioning

confidence: 99%

NSUN 3 and ABH 1 modify the wobble position of mt‐t RNA ^Met to expand codon recognition in mitochondrial translation

et al. 2016

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“…It presumably consists of mitochondrial tRNAs with chain-lengths of around 70 nucleotides, and, perhaps in part of cytoplasmic tRNAs which came from the cytoplasm by import or by contamination. The possibility of tRNA import from the cytoplasm is not excluded because we have previousaly detected cytoplasmic tRNAMe' in mitoplasts prepared by the same procedures as described here [22], although cytoplasmic tRNAPh' is not detected in either mitochondria or mitoplasts, as shown in Fig. 4a.…”

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confidence: 74%

Existence of nuclear‐encoded 5S‐rRNA in bovine mitochondria

et al. 1994

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A number of proteins functioning in mitochondria are synthesized in the cytoplasm and imported into the mitochondria via specific transport systems. In mammals, on the contrary, mitochondrial membranes have generally been considered to be impermeable to nucleic acids. However, here we show that an RNA with 120 nucleotides, the sequence of which is identical to that of the nuclear-encoded 5s RNA, exists in bovine mitochondria, although the mitochondrial genome encodes no 5s RNA gene. This RNA molecule was found to be retained in purified bovine mitochondria as well as in the mitoplasts, even after extensive treatment with an RNase, demonstrating that the 5s RNA is actually located inside the mitochondrial inner membrane. The 5s rRNA molecule was also shown to exist in mitochondria from rabbit and chicken.

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“…Except for these species, however, a single tRNA Met is encoded in animal mtDNAs in general (37). Mammalian mt tRNA Met has 5-formylcytidine at the wobble position (38), which enables the decoding of AUA in addition to AUG through 5-formylcytidine: A base pairing (39 -41). 5-Formylcytidine is a cytidine modification that allows the CAU anticodon to expand its decoding capability and recognize the AUA codon.…”

Section: Discussionmentioning

confidence: 99%

Taurine-containing Uridine Modifications in tRNA Anticodons Are Required to Decipher Non-universal Genetic Codes in Ascidian Mitochondria

Suzuki

Miyauchi

Yokobori

et al. 2011

Journal of Biological Chemistry

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Non-universal codons are known to be used in the mitochondrial (mt) 3 genetic code (1-6). DNA sequencing of proteincoding genes in various metazoan mtDNAs followed by comparison of the deduced amino acid sequences with those of other species revealed amino acid assignment deviations for the codons UGA, AUA, AGR, and AAA. The termination codon UGA in the universal genetic code specifies Trp in the mitochondria of all species investigated so far (1, 2). The AUA codon for Ile changes to specify Met in most metazoa except echinoderms, planaria, and coelenterates (2-4). AGR codons are used for Ser in most invertebrates, for Gly in urochordates, and for termination in vertebrates (7-10). The AAA codon specifies Asn in echinoderms (7) and platyhelminths (11).Our group previously reported that the mitochondrial decoding system of ascidian Halocynthia roretzi employs four non-universal genetic codes: UGA for Trp, AUA for Met and AGR for Gly (Table 1) (9, 12). Sequence analysis of H. roretzi mtDNA identified three tDNAs responsible for these non-universal codons. Each of these tDNAs contains thymidine (T) at the first (wobble) position of their anticodons (Table 1). Because an unmodified U at the wobble position can decode any of the four bases at the third letter of the codon, according to the mitochondrial four-way wobble rule (5, 13), the uridines of these tRNAs at the wobble position must be modified in order to decipher their respective non-universal genetic codes accurately. To elucidate the molecular mechanism of the decoding system, it is necessary to determine the chemical structure of the anticodon wobble base in H. roretzi mt tRNAs. We previously reported 5-carboxymethylaminomethyluridine at the wobble position of mt tRNA Met (AUR) from H. roretzi (14). However, the nucleotide identification was inaccurate because it was analyzed by conventional two-dimensional TLC, and the modification was determined based on a comparison of its rate of flow value with that of known modified nucleotides (15). In addition, we also reported that H. roretzi mt tRNA Gly -(AGR) has an unidentified modified U at the wobble position (16). We describe here the chemical structures of the wobble bases in mt tRNAs for non-universal genetic codes in the H. roretzi mitochondrial decoding system and discuss evolutionary insights into the role of wobble modification in genetic code alteration. EXPERIMENTAL PROCEDURESIsolation of mt tRNAs-Two hundred grams of the commercially available edible muscle of an ascidian, H. roretzi, was minced, and the tRNA fraction was obtained by phenol extraction as described previously (17). Two thousand A 260 units of crude tRNA were separated by the DEAE-cellulose column * This work was supported by grants-in-aid for scientific research (C) from The Japan Society for the Promotion of Science (to K. W.) and by grants-in-aid for scientific research on priority areas from the Ministry of Education, Science, Sports, and Culture of Japan (to Takeo Suzuki and Tsutomu Suzuki). □ S The on-line version of this article...

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A Novel Modified Nucleoside Found at the First Position of the Anticodon of Methionine tRNA from Bovine Liver Mitochondria

Cited by 107 publications

References 26 publications

NSUN 3 and ABH 1 modify the wobble position of mt‐t RNA ^Met to expand codon recognition in mitochondrial translation

NSUN 3 and ABH 1 modify the wobble position of mt‐t RNA ^Met to expand codon recognition in mitochondrial translation

Existence of nuclear‐encoded 5S‐rRNA in bovine mitochondria

Taurine-containing Uridine Modifications in tRNA Anticodons Are Required to Decipher Non-universal Genetic Codes in Ascidian Mitochondria

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A Novel Modified Nucleoside Found at the First Position of the Anticodon of Methionine tRNA from Bovine Liver Mitochondria

Cited by 107 publications

References 26 publications

NSUN 3 and ABH 1 modify the wobble position of mt‐t RNA Met to expand codon recognition in mitochondrial translation

NSUN 3 and ABH 1 modify the wobble position of mt‐t RNA Met to expand codon recognition in mitochondrial translation

Existence of nuclear‐encoded 5S‐rRNA in bovine mitochondria

Taurine-containing Uridine Modifications in tRNA Anticodons Are Required to Decipher Non-universal Genetic Codes in Ascidian Mitochondria

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NSUN 3 and ABH 1 modify the wobble position of mt‐t RNA ^Met to expand codon recognition in mitochondrial translation

NSUN 3 and ABH 1 modify the wobble position of mt‐t RNA ^Met to expand codon recognition in mitochondrial translation