Distribution of both lengths and 5' terminal nucleotides of mammalian pre-tRNA 3' trailers reflects properties of 3' processing endoribonuclease

Nashimoto, Masayuki

doi:10.1093/nar/25.6.1148

Cited by 79 publications

(79 citation statements)

References 29 publications

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“…7444C3 U, on the other hand, produces a cleavage product that would have one U protruding beyond the discriminator. This protruding U could be removed by tRNase Z (15), but this type of polishing by tRNase Z appears to be inefficient (Fig. 5, panel D).…”

Section: Discussionmentioning

confidence: 99%

“…Mature tRNA is not a substrate for 3Ј end processing (15)(16)(17); indeed, CCA of mature tRNA functions as a tRNase Z processing anti-determinant (but see Schiffer et al (18) for opposite results). The mechanism of CCA anti-determination has not been ascertained, but residues around the tRNase Z active site may form a rigid binding and exit channel for the tRNA 3Ј end trailer, cooperating with nucleotides directly after the discriminator to regulate pre-tRNA catalysis (20).…”

Section: Discussionmentioning

confidence: 99%

“…The CCA anti-determinant effect characterized in processing extracts and active fractions from mammalian and fruit fly cells (15,16) was confirmed with expressed tRNase Z from Bacillus subtilis (17) but was not observed with expressed tRNase Z from Arabidopsis thaliana or Methanococcus jannaschii (18).…”

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confidence: 89%

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Naturally Occurring Mutations in Human Mitochondrial Pre-tRNASer(UCN) Can Affect the Transfer Ribonuclease Z Cleavage Site, Processing Kinetics, and Substrate Secondary Structure

Yan¹,

Zareen²,

Levinger

2006

Journal of Biological Chemistry

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tRNAs are transcribed as precursors with a 5 end leader and a 3 end trailer. The 5 end leader is processed by RNase P, and in most organisms in all three kingdoms, transfer ribonuclease (tRNase) Z can endonucleolytically remove the 3 end trailer. Long ( L ) and short ( S ) forms of the tRNase Z gene are present in the human genome. tRNase Z L processes a nuclear-encoded pre-tRNA ϳ1600-fold more efficiently than tRNase Z S and is predicted to have a strong mitochondrial transport signal. tRNase Z L could, thus, process both nuclear-and mitochondrially encoded pre-tRNAs. More than 150 pathogenesis-associated mutations have been found in the mitochondrial genome, most of them in the 22 mitochondrially encoded tRNAs. All the mutations investigated in human mitochondrial tRNA Ser(UCN) affect processing efficiency, and some affect the cleavage site and secondary structure. These changes could affect tRNase Z processing of mutant pre-tRNAs, perhaps contributing to mitochondrial disease.Mitochondria, the intracellular organelles responsible for most of a eukaryotic cell energy production, possess their own maternally inherited genome. The circular 16,568-base pair human mitochondrial genome (1) is bidirectionally transcribed into long polycistronic heavy (H) 4 -and light (L)-strand precursor RNAs. Two rRNAs and 11 mRNAs encoding 13 polypeptides (all of them subunits of complexes in the respiratory transport chain) are punctuated by 22 tRNAs (1 tRNA for each of 18 amino acids and 2 each for leucine and serine with different anticodons) with very little intergenic RNA (2, 3). Several thousand additional polypeptides required for mitochondrial metabolism are nuclear-encoded, cytoplasmically translated and imported.Precursor tRNA transcripts have a 5Ј end leader and a 3Ј end trailer. Eukaryotic nuclear-encoded tRNAs are transcribed from RNA polymerase III promoters with short 5Ј end leaders and 3Ј end trailers ending with a U 3 tail. The characteristic length and sequence of mitochondrial pre-tRNA leaders and trailers, on the other hand, depend on the setting of individual tRNAs among the neighboring functional RNA units (other tRNAs, mRNAs, rRNAs) on the long polycistronic H-and L-strand transcripts (4).The 5Ј end leader is removed from pre-tRNAs by RNase P in a largely conserved, well characterized reaction (5). On the other hand, there are different paths to a mature tRNA 3Ј end (6). In the tRNAs of some prokaryotes, CCA is transcriptionally encoded, and the 3Ј end trailer is removed by the sequential activity of an endonuclease (RNase E) and exonucleases (7,8). In contrast, in most organisms in all three kingdoms and in extranuclear organelles, CCA is not transcriptionally encoded and can be added to the discriminator (the unpaired nucleotide after the 3Ј end of the acceptor stem, which is retained in mature tRNA) after precise endonucleolytic removal of the 3Ј end trailer by tRNase Z (9 -14).Intriguingly, CCA is a tRNase Z anti-determinant that prevents mature tRNA from recycling through tRNase Z, thus ensuring that ...

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Naturally Occurring Mutations in Human Mitochondrial Pre-tRNASer(UCN) Can Affect the Transfer Ribonuclease Z Cleavage Site, Processing Kinetics, and Substrate Secondary Structure

Yan¹,

Zareen²,

Levinger

2006

Journal of Biological Chemistry

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“…10 Additional contacts with the acceptor stem and 3' end trailer [11][12][13] suggest a structural basis for the CCA anti-determinant, which prevents tRNA from recycling through tRNase Z cleavage after CCA addition. [14][15][16] The Flexible Arm (FA), extruded from the body of tRNase Z, 11,17 confers tRNA-binding specificity. tRNase Z L may have evolved from a tandem gene duplication of tRNase Z S (reviewed in ref.…”

Section: Introductionmentioning

confidence: 99%

Effects of conserved D/T loop substitutions in the pre-tRNA substrate on tRNase Z catalysis

Hopkinson

Levinger²

2008

RNA Biology

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© 2 0 0 8 L A N D E S B I O S C I E N C E . D O N O T D I S T R I B U T E .tRNAs are transcribed as precursors with a 5' end leader and a 3' end trailer. In the course of tRNA maturation, RNase P removes the 5' end leader and tRNase Z can endonucleolytically remove the 3' end trailer. A domain remote from the active site of tRNase Z recognizes and binds substrate, principally through contacts with the elbow (D/T loops) of the tRNA. To evaluate possible contacts, processing kinetics was performed using human nuclear encoded pre-tRNA Arg with substitutions in conserved D and T loop nucleotides. Changes in K M observed with some of the substitutions suggest contacts between tRNase Z and substrate tRNA in this region, and changes in tRNA structure provide an additional basis for interpretation of the kinetic effects.

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“…1 tRNase Z is one of the tRNA-maturing enzymes, which removes a 3 0 trailer from pre-tRNA. [2][3][4] Most tRNase Zs cleave pre-tRNAs immediately downstream of a discriminator nucleotide, onto which the CCA residues are added to produce mature tRNA, whereas tRNase Z from Thermotoga maritima exceptionally cleaves pre-tRNAs containing the CCA sequence precisely after the A residue to create the mature 3 0 -termini. 5 tRNase Zs can be divided into two groups: a short form (tRNase Z S ) that consists of 300-400 amino acids and a long form (tRNase Z L ) that contains 800-900 amino acids.…”

Section: Introductionmentioning

confidence: 99%

Gene silencing by the tRNA maturase tRNase ZL under the direction of small-guide RNA

et al. 2006

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We have been developing a unique system for the downregulation of a gene expression through cutting a specific mRNA by the long form of tRNA 3 0 -processing endoribonuclease (tRNase Z L ) under the direction of small-guide RNA (sgRNA). However, the efficacy of this system and the involvement of tRNase Z L in the living cells were not clear. Here we show, by targeting the exogenous luciferase gene, that the efficacy of the sgRNA/tRNase Z L method can become comparable to that of the RNA interference technology and that the gene silencing is owing to tRNase Z L directed by sgRNA not owing to a simple antisense effect. We also show that tRNase Z L together with sgRNA can downregulate expression of the endogenous human genes Bcl-2 and glycogen synthase kinase-3b by degrading their mRNAs in cell culture. Furthermore, we demonstrate that a gene expression in the livers of postnatal mice can be inhibited by an only seven-nucleotide sgRNA. These data suggest that sgRNA might be utilized as therapeutic agents to treat diseases such as cancers and AIDS.

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Distribution of both lengths and 5' terminal nucleotides of mammalian pre-tRNA 3' trailers reflects properties of 3' processing endoribonuclease

Cited by 79 publications

References 29 publications

Naturally Occurring Mutations in Human Mitochondrial Pre-tRNASer(UCN) Can Affect the Transfer Ribonuclease Z Cleavage Site, Processing Kinetics, and Substrate Secondary Structure

Naturally Occurring Mutations in Human Mitochondrial Pre-tRNASer(UCN) Can Affect the Transfer Ribonuclease Z Cleavage Site, Processing Kinetics, and Substrate Secondary Structure

Effects of conserved D/T loop substitutions in the pre-tRNA substrate on tRNase Z catalysis

Gene silencing by the tRNA maturase tRNase ZL under the direction of small-guide RNA

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