Dataset Information

NSUN6 is a human RNA methyltransferase that catalyzes formation of m5C72 in specific tRNAs.

ABSTRACT: Many cellular RNAs require modification of specific residues for their biogenesis, structure, and function. 5-methylcytosine (m(5)C) is a common chemical modification in DNA and RNA but in contrast to the DNA modifying enzymes, only little is known about the methyltransferases that establish m(5)C modifications in RNA. The putative RNA methyltransferase NSUN6 belongs to the family of Nol1/Nop2/SUN domain (NSUN) proteins, but so far its cellular function has remained unknown. To reveal the target spectrum of human NSUN6, we applied UV crosslinking and analysis of cDNA (CRAC) as well as chemical crosslinking with 5-azacytidine. We found that human NSUN6 is associated with tRNAs and acts as a tRNA methyltransferase. Furthermore, we uncovered tRNA(Cys) and tRNA(Thr) as RNA substrates of NSUN6 and identified the cytosine C72 at the 3' end of the tRNA acceptor stem as the target nucleoside. Interestingly, target recognition in vitro depends on the presence of the 3'-CCA tail. Together with the finding that NSUN6 localizes to the cytoplasm and largely colocalizes with marker proteins for the Golgi apparatus and pericentriolar matrix, our data suggest that NSUN6 modifies tRNAs in a late step in their biogenesis.

SUBMITTER: Haag S

PROVIDER: S-EPMC4536315 | biostudies-literature | 2015 Sep

REPOSITORIES: biostudies-literature

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NSUN6 is a human RNA methyltransferase that catalyzes formation of m5C72 in specific tRNAs.

Haag Sara S Warda Ahmed S AS Kretschmer Jens J Günnigmann Manuel A MA Höbartner Claudia C Bohnsack Markus T MT

RNA (New York, N.Y.) 20150709 9

Many cellular RNAs require modification of specific residues for their biogenesis, structure, and function. 5-methylcytosine (m(5)C) is a common chemical modification in DNA and RNA but in contrast to the DNA modifying enzymes, only little is known about the methyltransferases that establish m(5)C modifications in RNA. The putative RNA methyltransferase NSUN6 belongs to the family of Nol1/Nop2/SUN domain (NSUN) proteins, but so far its cellular function has remained unknown. To reveal the target ...[more]

PMID: 26160102

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Project description:BackgroundPancreatic cancer (PC) is one of the most lethal solid malignancies in the world due to its excessive cell proliferation and aggressive metastatic features. Emerging evidences revealed the importance of posttranscriptional modifications of RNAs in PC progression. However, knowledge about the 5-methylcytosine (m5C) RNA modification in PC is still extremely limited. In this study, we attempted to explore the expression changes and clinical significances of 12 known m5C-related genes among PC patients.MethodsA total of 362 normal and 382 tumor specimens from PC patients were examined for candidate m5C-related gene and protein expression by using quantitative PCR (qPCR) and immunohistochemistry (IHC). The proliferation rate of PC cells was detected by MTS assay. Xenograft mouse models were used to assess the role of NSUN6 in PC tumor formation.FindingsThrough analyzing the four Gene Expression Omnibus (GEO) databases, six m5C-related genes shown significant and consistent alterations were selected for further examination in our 3 independent PC cohorts. Finally, we identified the reduction of NSUN6 as a common feature of all PC sample sets examined. NSUN6 expression correlated with clinicopathologic parameters including T stage, and Ki67+ cell rate. Further assessing the transcriptional profiles of 50 PC tissues, we found biological processes associated with cell proliferation like cell cycle and G2M checkpoint were enriched in NSUN6 lower expression group. Helped by in vitro PC cell lines and in vivo xenograft mouse models, we confirmed the role of NSUN6 in regulating cell proliferation and PC tumor growth. Last but also importantly, we also show the good performance of NSUN6 in evaluating tumor recurrence and survival among PC patients.InterpretationOur data suggested that NSUN6 is an important factor involved in regulating cell proliferation of PC, and highlights the potential of novel m5C-based clinical modalities as a therapeutic approach in PC patients.FundingThis study was supported by the National Natural Science Foundation of China (Grant Nos. 81803014, 81802424, and 81802911).

Dataset Information

NSUN6 is a human RNA methyltransferase that catalyzes formation of m5C72 in specific tRNAs.

Publications

NSUN6 is a human RNA methyltransferase that catalyzes formation of m5C72 in specific tRNAs.

Similar Datasets

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