TRNA genes

McBryant, S.J., E.E. Baird, J.W. Trauger, P.B. Dervan, and J.M. Gotteseeld. Minor groove DNA-protein contacts upstream of a tRNA gene detected with a synthetic DNA binding ligand. /. Mol. Biol. 1999, 286, 973-981. 

J. T. Sullivan and C. W. Ronson, Evolution of rhizobia by acquisition of a 500 kb symbiosis island that integrates into a pbe-tRNA gene. Proc. Natl. Acad. Sci. U.S.A. 95 5145-5149 (1998). 

Pestova, T. V., and Hellen, C. U. (2003). Translation elongation after assembly of ribosomes on the Cricket paralysis virus internal ribosomal entry site without initiation factors or initiator tRNA. Genes Dev. 17, 181—186. 

Frameshift suppression is also possible. This can be achieved by a second mutation in a tRNA gene such that the anticodon of a tRNA molecule consists of 4 bases rather than 3, for example, an extra C residue in the CCC anticodon sequence of a glycine tRNA gene. This change will allow correction of a +1 frameshift involving the GGG codon for glycine (Bossi, 1985). 

MERRF (myoclonic epilepsy with ragged red fibers) Is characterized by weakness on exertion, ataxia, and associated deafness and Is due to mutation of the mitochondrial tRNA gene. 

MELAS (mitochondrial encephalomyopathy with lactic acidosis and stroke-like episodes) resuits from a point mutation in the mitochondriai tRNA gene. 

When a mutation introduces a termination codon in the interior of a gene, translation is prematurely halted and the incomplete polypeptide is usually inactive. These are called nonsense mutations. The gene can be restored to normal function if a second mutation either (1) converts the misplaced termination codon to a codon specifying an amino acid or (2) suppresses the effects of the termination codon. Such restorative mutations are called nonsense suppressors they generally involve mutations in tRNA genes to produce altered (suppressor) tRNAs that can recognize the termination codon and insert an amino acid at that position. Most known suppressor tRNAs have single base substitutions in their anticodons. 

Suppressor tRNAs constitute an experimentally induced variation in the genetic code to allow the reading of what are usually termination codons, much like the naturally occurring code variations described in Box 27-2. Nonsense suppression does not completely disrupt normal information transfer in a cell, because the cell usually has several copies of each tRNA gene some of these duplicate genes are weakly expressed and account for only a minor part of the cellular pool of a particular tRNA. Suppressor mutations usually involve a minor tRNA, leaving the major tRNA to read its codon normally. 

Figure 5-34 (A) Two conformations of a segment of the yeast phenylalanine tRNA gene. The segment shown codes for the 3 end of the tRNA molecule shown in Fig. 5-30, including the T /C loop. (B) Formation of H-DNA (Fig. 5-24) proposed for a sequence in plasmid pGG32. The major element of the structure is the triplex, which is formed from the Watson-Crick duplex ( ) associated with the homopyrimidine loop through Hoogsteen base pairing (o, +). One of the two possible "isomeric" forms is shown. See Mirkin et al.378...

The 3 -terminal group of three nucleotides, CCA, is invariant among all tRNA molecules and is labile, undergoing active removal and resynthesis. The rate of this turnover is sufficient to involve about 20% of the tRNA molecules of a cell per generation, but it is very much slower than the rate of participation of the tRNA molecules in protein synthesis. The physiological significance of end turnover is unknown.233 While this CCA sequence is encoded in bacterial tRNA genes, it is added in a separate reaction in eukaryotes.234... 

Part of DNA sequence extending past the CCA end of the tRNA gene... 

Figure 28-10 Sequence of an E. coli tyrosine tRNA precursor drawn in a hypothetical secondary structure. Nucleotides found modified in the mature tRNA are indicated with their modifications (S4, 4-thiouridine Gm, 2 -0-methylgua-nosine 1°, N6-isopentenyladenosine jt, pseudouridine T, ribothymidine see also Fig. 5-33).241 A partial sequence of the tRNA gene past the CCA end is also shown. Note the region of local 2-fold rotational symmetry (indicated by the bars and the dot). The anticodon 3 -CUA (shaded) of this suppressor tRNA pairs with termination codon 5 -UAG.

Cleavage at the 5 end of the 5.8S region requires RNase MRP, a relative of the RNase P that cleaves at the 5 ends of tRNAs (Fig. 28-10).525 547 MRP (mitochondrial processing protein) also cleaves primers for mitochondrial DNA replication. The importance of the enzyme is emphasized by the existence of a hereditary defect in the MRP RNA (Table 28-3) that causes abnormalities in bone, cartilage, hair, and the immune system.5473 Most bacterial rRNA genes have a tRNA gene in the position corresponding to that of 5.8S RNA... 

Most eukaryotic tRNAs are formed from monomeric precursors, each gene acting as a transcriptional unit. Processing is similar to that in bacteria (Section A, 7). Eukaryotic RNase P usually cleaves the 5 end,555-558c and another enzyme cuts at the 3 end.542 556 The 3 CCA sequence of the mature tRNA is usually not present in the primary transcript but is added.559/559a b As in bacteria (p. 1620) extensive modification of bases also occurs in the tRNA precursors of eukaryotes.235 560-562 Many tRNA genes contain introns, which must be removed by splicing (Section 5). 

Most nonsense suppressor genes are mutants of tRNA genes. In view of this fact, how can cells survive the presence of such mutations ... 

PolIII polymerase also transcribes tRNA genes. In this case TFIIIA does not participate in the transcription process (see fig. 28.12c). 

A typical rRNA (rrn) operon contains two promoters and genes for 16S, 23S, and 5S rRNA and a single 4S tRNA gene. The four fully processed RNAs are derived from a single intact 30S primary transcript. 

Point Mutations in rRNA/tRNA Genes of mtDNA Associated with Mitochondrial Diseases 2... 

A number of distinctive syndromes have been shown to be associated with specific point mutations of mtDNA (Table 1) (M15, S4, S14). Several point mutations have been reported to occur at tRNA genes in the mitochondrial genome. For example, the A8344G mutation is present in patients with MERRF syndrome (S9), whereas the A3243G mutation of mtDNA was first identified in a subgroup of patients with MELAS syndrome (G4). MERRF syndrome was the first... 

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