Ethnic differences in frequencies of gene polymorphisms in the MYCL1 region and modulation of lung cancer patients’ survival

Spinola, Monica; Falvella, Felicia Stefania; Galvan, Antonella; Pignatiello, Carmen; Leoni, Vera P.; Pastorino, Ugo; Paroni, Rita; Chen, Shuqing; Skaug, Vidar; Haugen, Aage; Dragani, Tommaso A.

doi:10.1016/j.lungcan.2006.10.023

Cited by 24 publications

(23 citation statements)

References 16 publications

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“…PTU treatment repressed expression of THRSP ␣ (a thyroid hormone responsive transcription factor) , a Na + /glucose symporter (MFSD2) (Spinola et al, 2007) and a folate transporter (SLC19A1) (Qiu et al, 2006). The remaining common genes enhanced by PTU include five genes involved in lipid metabolism (ANGPTL3, ACAA1, ADFP, PHOSPHO1 and PTGDS).…”

Section: Discussionmentioning

confidence: 99%

Manipulation of thyroid status and/or GH injection alters hepatic gene expression in the juvenile chicken

Wang

Carré

Saxton

et al. 2007

Cytogenet Genome Res

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Both thyroid hormone (T₃) and growth hormone (GH) are important regulators of somatic growth in birds and mammals. Although T₃-mediated gene transcription is well known, the molecular basis of T₃interaction with GH on growth and development of birds remains unknown. In earlier studies, we discovered that exogenous GH alone increased accumulation of visceral fat in young chickens, while the combination of GH injections and dietary T₃ worked synergistically to deplete body fat. In the present study, cDNA microarray and quantitative RT-PCR analyses enabled us to examine hepatic gene expression in young chickens after chronic manipulation of thyroid status and GH injection alone or in combination with T₃. Thyroid status modulates expression of common and unique sets of genes involved in a wide range of molecular functions (i.e., energy metabolism, storage and transport, signal transduction, protein turnover and drug detoxification). Hepatic expression of 35 genes was altered by hypothyroidism (e.g., ADFP, ANGPTL3, GSTΑ, CAT, PPARG, HMGCL, GHR, IGF1, STAT3, THRSPα), whereas hyperthyroidism affected expression of another cluster of 13 genes (e.g., IGFBP1, KHK, LDHB, BAIA2L1, SULT1B, TRIAD3). Several genes were identified which have not been previously ascribed as T₃ responsive (e.g., DEFB9, EPS8L2, ARHGAP1, LASS2, INHBC). Exogenous GH altered expression of 17 genes (e.g., CCAR1, CYP2C45, GYS2, ENOB, HK1, FABP1, SQLE, SOCS2, UPG2). The T₃+GH treatment depleted the greatest amount of body fat, where 34 differentially expressed genes were unique to this group (e.g., C/EBP, CDC42EP1, SYDE2, PCK2, PIK4CA, TH1L, GPT2, BHMT). The marked reduction in body fat brought about by the T₃+GH synergism could involve modulation of hormone signaling via altered activity of the Ras superfamily of molecular switches, which control diverse biological processes. In conclusion, this study provides the first global analysis of endocrine (T₃ and GH) regulation of hepatic gene transcription in the chicken.

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Section: Discussionmentioning

confidence: 99%

Manipulation of thyroid status and/or GH injection alters hepatic gene expression in the juvenile chicken

Wang

Carré

Saxton

et al. 2007

Cytogenet Genome Res

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“…TRIT1 is particularly interesting due to its role as a putative lung adenocarcinoma tumor suppressor, as its expression was significantly down regulated in lung adenocarcinomas (Spinola et al 2005). A genome-wide association study of a single nucleotide polymorphism (SNP) mapping to TRIT1, in different ethnic populations, demonstrated statistically significant links between a TRIT1 Phe202Leu genotype and lung cancer survival rates (Spinola et al 2007). This suggests that ian association of leucine codon usage and tRNA isopentenyl transferase activity may be highly conserved well beyond the bacterial domain.…”

Section: Implications For Comparative Functional Genomics Of Trna Isomentioning

confidence: 99%

The i⁶A37 tRNA modification is essential for proper decoding of UUX-Leucine codons during rpoS and iraP translation

Aubee

Olu

Thompson

2016

RNA

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The translation of rpoS (σ S ), the general stress/stationary phase sigma factor, is tightly regulated at the post-transcriptional level by several factors via mechanisms that are not clearly defined. One of these factors is MiaA, the enzyme necessary for the first step in the N 6 -isopentyl-2-thiomethyladenosinemethyladenosine 37 (ms 2 i 6 A37) tRNA modification. We tested the hypothesis that an elevated UUX-Leucine/total leucine codon ratio can be used to identify transcripts whose translation would be sensitive to loss of the MiaA-dependent modification. We identified iraP as another candidate MiaA-sensitive gene, based on the UUX-Leucine/ total leucine codon ratio. An iraP-lacZ fusion was significantly decreased in the absence of MiaA, consistent with our predictive model. To determine the role of MiaA in UUX-Leucine decoding in rpoS and iraP, we measured β-galactosidasespecific activity of miaA − rpoS and iraP translational fusions upon overexpression of leucine tRNAs. We observed suppression of the MiaA effect on rpoS, and not iraP, via overexpression of tRNA LeuX but not tRNA LeuZ . We also tested the hypothesis that the MiaA requirement for rpoS and iraP translation is due to decoding of UUX-Leucine codons within the rpoS and iraP transcripts, respectively. We observed a partial suppression of the MiaA requirement for rpoS and iraP translational fusions containing one or both UUX-Leucine codons removed. Taken together, this suggests that MiaA is necessary for rpoS and iraP translation through proper decoding of UUX-Leucine codons and that rpoS and iraP mRNAs are both modification tunable transcripts (MoTTs) via the presence of the modification.

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“…In lung tumors examined, TRIT1 mRNA levels were 6-to 14-fold lower than those in healthy lung (20). The tumorigenic potential of A549 cells in nude mice was reduced by ectopic expression of TRIT1 (20), and genetic linkage disequilibrium refined a region responsible for cancer progression on chromosome 1p34 that includes a TRIT1 rare mutation allele associated with poor survival in some ethnic groups (21). Human TRIT1 was confirmed to be an IPTase by complementation of a suppressor tRNA Ser UCA-mediated phenotype in mod5-deficient S. cerevisiae (20) and by a direct IPTase activity assay of recombinant TRIT1 protein (18).…”

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confidence: 94%

Human Cells Have a Limited Set of tRNA Anticodon Loop Substrates of the tRNA Isopentenyltransferase TRIT1 Tumor Suppressor

Lamichhane

Mattijssen

Maraia

2013

Molecular and Cellular Biology

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Human TRIT1 is a tRNA isopentenyltransferase (IPTase) homologue of Escherichia coli MiaA, Saccharomyces cerevisiae Mod5, Schizosaccharomyces pombe Tit1, and Caenorhabditis elegans GRO-1 that adds isopentenyl groups to adenosine 37 (i6A37) of substrate tRNAs. Prior studies indicate that i6A37 increases translation fidelity and efficiency in codon-specific ways. TRIT1 is a tumor suppressor whose mutant alleles are associated with cancer progression. We report the systematic identification of i6A37-containing tRNAs in a higher eukaryote, performed using small interfering RNA knockdown and other methods to examine TRIT1 activity in HeLa cells. Although several potential substrates contained the IPTase recognition sequence A36A37A38 in the anticodon loop, only tRNA Ser AGA, tRNA Ser CGA, tRNA Ser UGA, and selenocysteine tRNA with UCA (tRNA [Ser]Sec UCA) contained i6A37. This subset is a significantly more restricted than that for two distant yeasts (S. cerevisiae and S. pombe), the only other organisms comprehensively examined. Unlike the fully i6A37-modified tRNAs for Ser, tRNA[Ser]Sec UCA is partially (ϳ40%) modified. Exogenous selenium and other treatments that decreased the i6A37 content of tRNA [ T ranslation of mRNA should be faithful in order to produce functional proteins, as codon misreading can lead to misfolding and aggregation, yet quality control must be balanced with speed and efficiency in fast-growing cells (1-3). Modifications of the tRNA anticodon loop at positions 34 and 37 contribute to efficiency and fidelity in a codon-specific manner. In addition, these modifications can extend or restrict the potential for wobble base recognition of cognate and noncognate codons and thus contribute to deciphering the genetic code (4,5). A deficiency of different types of tRNA wobble base U34 modification can have different mRNA-specific effects, with consequent effects on phenotypes, as different subsets of mRNAs are overenriched in the cognate codons (6)(7)(8). A link between tRNA modification and specific mRNA subsets was recently extended to the A37 position in the anticodon loop (9).Three types of complex modifications can exist at position 37: N 6 -isopentenyladenosine (i6A37); N 6 -threonylcarbamoyladenosine (t6A37) or its cyclized derivative, ct6A, in archaea and bacteria; and wybutosine (yW37). These are present in distinct subsets of tRNAs in all three domains of life (10-12). The importance of the A37 modification in mammals is illustrated by tRNA Lys UUU, which contains a methyl-sulfur derivative of t6A37, ms2t6A37. Cdkal1 was identified as an enzyme of unknown function that was associated with diabetes risk. It was later found to be the enzyme that adds the methylsulfur group to t6A37 of tRNA Lys UUU and that its deletion from pancreatic ␤ cells causes type 2 diabetes in mice (13,14).Evidence from the fission yeast Schizosaccharomyces pombe indicates that i6A37 increases the specific activity of its tRNAs, increasing fidelity at cognate codons, decreasing fidelity at noncognate codons, and promotin...

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Ethnic differences in frequencies of gene polymorphisms in the MYCL1 region and modulation of lung cancer patients’ survival

Cited by 24 publications

References 16 publications

Manipulation of thyroid status and/or GH injection alters hepatic gene expression in the juvenile chicken

Manipulation of thyroid status and/or GH injection alters hepatic gene expression in the juvenile chicken

The i⁶A37 tRNA modification is essential for proper decoding of UUX-Leucine codons during rpoS and iraP translation

Human Cells Have a Limited Set of tRNA Anticodon Loop Substrates of the tRNA Isopentenyltransferase TRIT1 Tumor Suppressor

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Ethnic differences in frequencies of gene polymorphisms in the MYCL1 region and modulation of lung cancer patients’ survival

Cited by 24 publications

References 16 publications

Manipulation of thyroid status and/or GH injection alters hepatic gene expression in the juvenile chicken

Manipulation of thyroid status and/or GH injection alters hepatic gene expression in the juvenile chicken

The i6A37 tRNA modification is essential for proper decoding of UUX-Leucine codons during rpoS and iraP translation

Human Cells Have a Limited Set of tRNA Anticodon Loop Substrates of the tRNA Isopentenyltransferase TRIT1 Tumor Suppressor

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The i⁶A37 tRNA modification is essential for proper decoding of UUX-Leucine codons during rpoS and iraP translation