ライフサイエンスコーパス: tRNA(Leu)

1 euRS, are required for editing of mischarged tRNALeu.

2 e folding of an Escherichia coli cytoplasmic tRNALeu.

3 nd interacts with the corner of the L-shaped tRNALeu.

4 ative stress, cleaving the anticodon loop of tRNA(Leu).

5 h ATP, AMP, or the terminal adenosine of the tRNA(Leu).

6 that DeltaAla(P) would be condensed with Leu-tRNA(Leu).

7 to significantly hydrolyze misaminoacylated tRNA(Leu).

8 es a TTA codon predicted to be recognized by tRNA(leu).

9 tation that hydrolyzes correctly charged Leu-tRNA(Leu).

10 e yielded a mutant LeuRS that hydrolyzes Leu-tRNA(Leu).

11 ions, including introns and the anticodon of tRNA(Leu).

12 show a decrease in the cellular abundance of tRNA(Leu).

13 T mutation in the leucine transfer RNA gene (tRNAleu)].

14 Mutations in the anticodon and extra arm of tRNALeu-1 do not measurably effect its ability to serve

15 wild type Leu-tRNALeu-4 (UAA) or mutant Leu-tRNALeu-4 (CUA) are each 0.4 +/- 0.2 microM.

16 een L/F-transferase and either wild type Leu-tRNALeu-4 (UAA) or mutant Leu-tRNALeu-4 (CUA) are each 0

17 to characterize the determinants of the Leu-tRNALeu-4 acceptor stem recognized by the L/F-transferas

18 itioning of G18 and G19 that is found in all tRNA(Leu); a base was inserted at position 47n between t

19 aled differences in the contributions of the tRNA(Leu) acceptor stem base-pairs to tRNA(Leu) function

20 ficity was contingent on the presence of the tRNA(Leu) acceptor stem sequence.

21 cyl-tRNA synthetase by formation of a stable tRNA(Leu)-AN2690 adduct in the editing site of the enzym

22 Herein, we describe the smallest tRNA(leu) analog that has been aminoacylated to a signif

23 A series of tRNA(leu) analogs with various domains and combinations

24 8ph by mutant H3S28A repressed Brf1, TBP and tRNA(Leu) and 5S rRNA expression and decreased occupancy

25 cer cells (MCF-7) decreases the induction of tRNA(Leu) and 5S rRNA genes by alcohol, whereas reductio

26 Reduction of Brf1 significantly decreased tRNA(Leu) and 5S rRNA transcription and repressed EGF-in

27 induce H3S28ph, which, in turn, upregulates tRNA(Leu) and 5S rRNA transcription through Brf1 and TBP

28 EGFR, but not PI3K, reduced both H3S28ph and tRNA(Leu) and 5S rRNA transcription.

29 ced occupancy of H3S28ph in the promoters of tRNA(Leu) and 5S rRNA.

30 urnover, thus inhibiting synthesis of leucyl-tRNA(Leu) and consequentially blocking protein synthesis

31 Experiments monitoring deacylation of Ile-tRNA(Leu) and misactivated adenylate turnover revealed t

32 to disrupt hydrolytic editing of mischarged tRNA(Leu) and to result in variation within the proteome

33 ichia coli LeuRS abolished aminoacylation of tRNALeu and also amino acid editing of mischarged tRNA m

34 equence alters mitochondrial localization of tRNA(Leu), and in vivo studies also show a decrease in t

35 d containing three tRNA genes, tRNA(1)(Ser), tRNA(Leu), and tRNA(2)(Ser).

36 quence changes, as significant levels of Ile-tRNA(Leu) are formed in the presence of high concentrati

37 When the 3' end of tRNA(Leu) binds to the editing active site, the boron cr

38 Thus, these LeuRS mutants charge tRNA(Leu) but fail to translocate these products to the

39 uggested that other tRNAs can substitute for tRNA(Leu) but that interactions in addition to pairing o

40 ing function to correct misaminoacylation of tRNA(Leu) by isoleucine and methionine.

41 The rate of misaminoacylation of tRNA(Leu) by isoleucine and valine increases with the in

42 rase-dependent increase in the proportion of tRNA(Leu(CAA)) containing m(5)C at the wobble position,

43 constant of 22 nM for one of its substrates, tRNA(Leu)(CAG).

44 the substrate for the condensation with Leu-tRNA(Leu) catalyzed by the C-terminal domain of DhpH.

45 tRNA(Leu) charging decreased, but only small increases i

46 d an archaeal leucyl-tRNA synthetase (LeuRS):tRNA(Leu) complex.

47 The gene arrangement and lack of a tRNA(Leu(CUN)) gene in P. opilio is most parsimoniously

48 which probably destroyed the function of the tRNA(Leu(CUN)) gene.

49 cantly decreased use of codons recognized by tRNA(Leu(CUN)), likely due to selection to utilize the m

50 ochondrial tRNA genes and lacks the gene for tRNA(Leu(CUN)).

51 niversally conserved aspartic acid abolished tRNA(Leu) deacylation.

52 TrmK-catalyzed methylation of A22 mutants of tRNA(Leu) demonstrate that the adenine at position 22 is

53 tide linker and allows interactions with the tRNA(Leu) elbow.

54 limiting C-terminal domain accessibility to tRNA(Leu) facilitates its role in protein synthesis and

55 e is imported rapidly, while the mature-size tRNA(Leu) fails to be imported in this system.

56 ynthetase that accurately charges leucine to tRNA(Leu) for protein translation.

57 TM84 requires tRNA(Leu) for tight binding to the LeuRS synthetic activ

58 ermine the nucleotides that are required for tRNA(Leu) function.

59 of the tRNA(Leu) acceptor stem base-pairs to tRNA(Leu) function: in the type I, but not the type II f

60 thogenicity island (Pai) that is linked to a tRNA(Leu) gene found also in Pseudomonas aeruginosa but

61 e complete initiator tRNA(Met) gene, metY; a tRNA(Leu) gene; the tpiA gene product; and the MrsA prot

62 hat the association of BRF1 and pol III with tRNA(Leu) genes in cells decreases when ERK is inactivat

63 n in the occupancy of all TFIIIB subunits on tRNA(Leu) genes, whereas prolonged PTEN expression resul

64 es of tRNASer genes, 7 from five families of tRNALeu genes, and 3 from three families of tRNAAla gene

65 The trapping of enzyme-bound tRNA(Leu) in the editing site prevents catalytic turnove

66 tRNA acetylation leads to reduced levels of tRNA(Leu), increased ribosome stalling, and activation o

67 The substrate, composed of tRNA(Ser) and tRNA(Leu), is transcribed in tandem with a 59-nucleotide

68 so dispensable for hydrolysis of the charged tRNA(leu) mimics.

69 fer editing activity that efficiently clears tRNA(Leu) mischarged with isoleucine.

70 's post-transfer hydrolytic activity against tRNA(Leu) mischarged with methionine is weak.

71 ino acid residue in the presence of a mutant tRNA(Leu) molecule containing the extra nucleotide, U, a

72 ) aminoacylates up to six different class II tRNA(leu) molecules.

73 e II counterparts.A minimum of six conserved tRNA(Leu) nucleotides were required to change the amino

74 Binding of gold-labeled tRNA(Leu) places leucyl-tRNA synthetase and the bifuncti

75 sidue group I intron of the Anabaena PCC7120 tRNAleu precursor.

76 Using tRNA(Leu) purified from a DUS 2 knockout strain of yeast

77 .5-7.3 kb of dissimilar intervening DNA with tRNA(Leu)-queA-tgt sequences that are also found in Pseu

78 st enough to completely block mischarging of tRNA(Leu), resulting in codon ambiguity and statistical

79 leucine occurs through misaminoacylation of tRNALeu, similar to the misincorporation of norleucine f

80 RNA promoters, including that for the major tRNALeu species in Escherichia coli, tRNA1Leu.

81 a activity, but increased the k(cat) for Leu-tRNA(Leu) synthesis approximately 8-fold.

82 es in the variable loop and acceptor stem of tRNA(Leu)(TAA) are required for substrate digestion.

83 d velcrin treatment promotes the cleavage of tRNA(Leu)(TAA) by inducing PDE3A-SLFN12 complex formatio

84 Velcrin-induced cleavage of tRNA(Leu)(TAA) by SLFN12 and the concomitant global inhi

85 SLFN12 selectively digests tRNA(Leu)(TAA), and velcrin treatment promotes the cleav

86 sensitive cells results in downregulation of tRNA(Leu)(TAA), ribosome pausing at Leu-TTA codons and g

87 e physiological substrate of SLFN12 RNase is tRNA(Leu)(TAA).

88 ionally, we identified the cleavage sites of tRNALeu(TAA) generated by SLFN11 in cells and revealed t

89 Proteomic analysis suggests tRNALeu(TAA) influences proteins essential for maintaini

90 cer cells to DDAs by cleaving and decreasing tRNALeu(TAA) levels.

91 upon administration of DDAs, SLFN11 cleaves tRNALeu(TAA), triggering ER stress and protein aggregate

92 viated by SLFN11-knockout or transfection of tRNALeu(TAA).

93 es a single nucleotide in the anticodon of a tRNA(Leu) that changes its normal 5'CAG3' leucine antico

94 by proline and that sncB69 encodes a mutant tRNA(Leu) that corrects the mutation.

95 c tRNA loci (e.g., the nuclear tRNA(Gly) and tRNA(Leu), the mitochondrial tRNA(Val) and tRNA(Pro)) we

96 bstrate with a uridine at position 38 (human tRNA(Leu)), there was very slight formation of pseudouri

97 c precursors containing the tRNA(1)(Ser) and tRNA(Leu) transcripts with a 59-nucleotide intergenic se

98 RNA Pol III-dependent genes (Pol III genes), tRNA(Leu), tRNA(Tyr), 5S rRNA and 7SL RNA.

99 found to interrupt the anticodon loop of the tRNA(Leu)(UAA) gene in a bacterium belonging to the gamm

100 -proteobacteria, and the first instance of a tRNA(Leu)(UAA) group I intron to be found in a group of

101 and processing of the genes tRNA(Thr)(UGU), tRNA(Leu)(UAA), and tRNA(Phe) (GAA) therefore attributes

102 Many tRNA(Leu)UAA genes from plastids contain a group I intro

103 The phylogenetic distribution of the tRNA(Leu)UAA intron follows the clustering of rRNA seque

104 Our data support the notion that the tRNA(Leu)UAA intron was inherited by cyanobacteria and p

105 nd secondary structural similarities between tRNA(Leu)UAA introns found in strains of the cyanobacter

106 either does with other known cyanobacterial tRNA(Leu)UAA introns.

107 Extra copies of the tRNA(Leu)(UAG) gene rescued the cold sensitivity and in

108 ue, the levels of three point mutations, the tRNA(Leu(UUA)) 3243 mutation causing mitochondrial encep

109 In particular, the tRNA(Leu(UUR)) A3243G mutation causes mitochondrial ence

110 pathogenetic mechanism of the mitochondrial tRNA(Leu(UUR)) A3243G transition associated with the mit

111 ribosomes, possibly as a consequence of the tRNA(Leu(UUR)) aminoacylation defect.

112 75%) reduction in the level of aminoacylated tRNA(Leu(UUR)) and a decrease in mitochondrial protein s

113 high affinity wild-type and mutant human mt-tRNA(Leu(UUR)) and mt-tRNA(Lys), and stabilize mutant mt

114 ue to selection to utilize the more specific tRNA(Leu(UUR)) anticodon.

115 ate levels and the aminoacylated fraction of tRNA(Leu(UUR)) are likely to contribute to the decreases

116 by reduced the aminoacylated efficiencies of tRNA(Leu(UUR)) as well as tRNA(Ala) and tRNA(Met).

117 showed that the alteration of aminoacylation tRNA(Leu(UUR)) caused by the A3243G mutation led to mito

118 The T3271C mutation in tRNA(Leu(UUR)) did not affect the efficiency of aminoacy

119 ions of the mutation at position 3243 in the tRNA(Leu(UUR)) gene associated with the MELAS encephalom

120 zes a mtDNA segment within the mitochondrial tRNA(Leu(UUR)) gene immediately adjacent to and downstre

121 3G and T3271C mutations in the mitochondrial tRNA(Leu(UUR)) gene on the aminoacylation of tRNA(Leu(UU

122 ing analysis of the mtDNA segment within the tRNA(Leu(UUR)) gene that binds the transcription termina

123 ription termination region (TERM) within the tRNA(Leu(UUR)) gene was consistently and strongly protec

124 ated mutations are known to affect the hs mt tRNA(Leu(UUR)) gene, and the molecular-level properties

125 e if the decreased fraction of aminoacylated tRNA(Leu(UUR)) in A3243G mutant cells was due to a defec

126 in the amount of ND1 mRNA and co-transcribed tRNA(Leu(UUR)) in mutant cells.

127 f the D, TPsiC, and anticodon loops of hs mt tRNA(Leu(UUR)) in the structure and function of this mol

128 uences, indicating that this region of hs mt tRNA(Leu(UUR)) is not involved in recognition by LeuRS.

129 increasing heteroplasmy levels of the mtDNA tRNA(Leu(UUR)) nucleotide (nt) 3243A > G mutation result

130 ted either with the m.3243A>G mutation in mt-tRNA(Leu(UUR)) or with mutations in the mt-tRNA(Ile), bo

131 tion efficiencies among wild-type and mutant tRNA(Leu(UUR)) transcripts.

132 Native A3243G mutant tRNA(Leu(UUR)) was 25-fold less efficiently aminoacylate

133 S)-associated mt-tRNA leucine (Leu, UUR) (mt-tRNA(Leu(UUR))) species.

134 zed nucleotides in the loop regions of hs mt tRNA(Leu(UUR)), and tRNA variants that were aminoacylate

135 rs more structured than wild-type (WT) hs mt tRNA(Leu(UUR)), indicating that the entirely AU stem of

136 noacylation kinetics of wild-type and mutant tRNA(Leu(UUR)), using both native and in vitro transcrib

137 The results indicate that hs mt tRNA(Leu(UUR)), which is known to have structurally weak

138 ion was an inefficient aminoacylation of the tRNA(Leu(UUR)).

139 lated in vitro, compared to native wild-type tRNA(Leu(UUR)).

140 )) and mt-tRNA(Lys), and stabilize mutant mt-tRNA(Leu(UUR)).

141 , using both native and in vitro transcribed tRNA(Leu(UUR)).

142 creased steady-state levels of mitochondrial tRNA(Leu(UUR)).

143 tRNA(Leu(UUR)) gene on the aminoacylation of tRNA(Leu(UUR)).

144 a decrease in the fraction of aminoacylated tRNA(Leu(UUR)).

145 ially denatured for the wild type (WT) hs mt tRNALeu(UUR) and were significantly stabilized by mutati

146 as further elucidated with a mutant of hs mt tRNALeu(UUR) containing a stabilized D stem and a pathog

147 structure of the human mitochondrial (hs mt) tRNALeu(UUR) features several domains that are predicted

148 n at position 3256, within the mitochondrial tRNALeu(UUR) gene in a patient with a multisystem disord

149 process of charged and uncharged tRNALys and tRNALeu(UUR) has revealed that the separation of the two

150 tRNALeu(UUR), an etiologic hot spot for such diseases, h

151 ease in steady-state levels of mitochondrial tRNALeu(UUR), and a partial impairment of mitochondrial

152 n pattern was observed between the wild-type tRNALeu(UUR)and its counterpart carrying the A3243G muta

153 Complementary sequencing of tRNALeu(UUR)has allowed the localization of this modific

154 Mitochondrial DNA (mtDNA) 3243A > G tRNALeu((UUR)) heteroplasmic mutation (m.3243A > G) exhi

155 The expected tRNALeu-UUR gene was not revealed between COI and COII.

156 vivo and in vitro characteristics of type I tRNA(Leu) variants with their type II counterparts.A min

157 In this way, a group I intron located in tRNA(Leu), which has been used extensively for phylogene

158 anscript of the A14G pathogenic mutant of mt-tRNA(Leu), which is known to dimerize, and find that the

159 of tandem UAGA quadruplets by an engineered tRNA(Leu) with an eight-base anticodon loop, has been in

160 lation is facilitated by the misacylation of tRNA(Leu) with methionine by the methionyl-tRNA syntheta

161 allowing the enzyme to conditionally charge tRNA(Leu) with methionine.

162 The decoding properties of tRNA(Leu) with U at position 33.5 of its eight-membered