ライフサイエンスコーパス: tRNA(Leu)

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

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

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

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

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

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

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

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

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

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

11 75%) reduction in the level of aminoacylated tRNA(Leu(UUR)) and a decrease in mitochondrial protein s

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

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

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

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

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

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

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

19 8ph by mutant H3S28A repressed Brf1, TBP and tRNA(Leu) and 5S rRNA expression and decreased occupancy

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

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

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

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

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

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

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

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

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

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

30 e folding of an Escherichia coli cytoplasmic tRNALeu.

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

61 to significantly hydrolyze misaminoacylated tRNA(Leu).

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

63 euRS, are required for editing of mischarged tRNALeu.

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

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

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

67 3G and T3271C mutations in the mitochondrial tRNA(Leu(UUR)) gene on the aminoacylation of tRNA(Leu(UU

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

154 .5-7.3 kb of dissimilar intervening DNA with tRNA(Leu)-queA-tgt sequences that are also found in Pseu

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