Translation termination

Acatalasemia is a rare hereditary deficiency of tissue catalase and is inherited as an autosomal recessive trait (03). This enzyme deficiency was discovered in 1948 by Takahara and Miyamoto (Tl). Two different types of acatalasemia can be distinguished clinically and biochemically. The severe form, Japanese-type acatalasemia, is characterized by nearly total loss of catalase activity in the red blood cells and is often associated with an ulcerating lesion of the oral cavity. The asymptomatic Swiss-type acatalasemia is characterized by residual catalase activity with aberrant biochemical properties. In four unrelated families with Japanese-type acatalasemia, a splicing mutation due to a G-to-A transition at the fifth nucleotide in intron 4 was elucidated (K20, W5). We have also determined a single base deletion resulting in the frameshift and premature translational termination in the Japanese patient (HI6). 

D2. Daar, I. O., and Maquat, L. E., Premature translation termination mediates triosephosphate iso-merase mRNA degradation. Mol. Cell. Biol. 8,802-813 (1988). 

PSI] is the prion of Sup35p, a translation termination factor (Ter-Avanesyan et al., 1994 Wickner, 1994). Conversion of wild-type yeast cells to the infected state results in reduction of the termination activity and, consequendy, to a nonsense suppression phenotype. This property can be used to detect [PSI] by genetic selection (Fig. 2). Sup35p is an essential gene whose knockout leads to cell death. Therefore, it appears that the [PSI] condition corresponds to only partial inactivation of Sup35p and enough of the normal protein is left to avert cell death. 

Prion domain Middle domain Translation termination domain... 

PSI] nomenclature SUP35 Wild-type gene encoding a subunit of the translation termination factor... 

Activity of soluble protein Nitrogen catabolism regulation Translation termination Not known Not known Not known... 

As with Ure2p, expression of a Sup35p variant lacking the prion domain restores the translation termination activity of the full-length protein in... 

With few exceptions, the genetic code is universal. Codons in different organisms have identical meanings, specifying the insertion of one of the canonical 20 amino acids or translational termination. Although amino acids different from the canonical 20 have been discovered in some organisms, only two amino acids,... 

PTT is based on a combination of reverse-transcription polymerase chain reaction (RT-PCR) and linked in vitro transcription and translation (Fig. 3C). This combination of procedures can selectively detect translation-terminating or nonsense mutations. Unfortunately, it does not find missense mutations, which may be etiologic, depending upon location. 

Abbreviations aa-tRNA Amino-acyl tRNA eLF Eukaryotic translation initiation factor IF Prokaryotic translation initiation factor eEF Eukaryotic translation elongation factor EF Prokaryotic translation elongation factor eRF Eukaryotic translation termination factor (release factor) RF Prokaryotic translation release factor RRF Ribosome recycling factor Rps Protein of the prokaryotic small ribosomal subunit Rpl Protein of the eukaryotic large ribosomal subunit S Protein of the prokaryotic small ribosomal subunit L Protein of the prokaryotic large ribosomal subunit PTC Peptidyl transferase center RNC Ribosome-nascent chain-mRNA complex ram Ribosomal ambiguity mutation RAC Ribosome-associated complex NMD Nonsense-mediated mRNA decay... 

Errors in translation termination premature termination and readthrough... 

While readthrough is usually a detrimental process, in some cases it can help to suppress problems, e.g. arising from premature stop codons present on the DNA level. This type of readthrough, also termed nonsense suppression, leads to the generation of a fraction of the full length protein in addition to the shortened version. Omnipotent suppressors cause nonsense suppression of all three termination codons. In this process, a near cognate tRNA successfully competes with the termination factors such that amino acid incorporation rather than premature termination of translation occurs. Omnipotent suppression can be caused by mutations in various factors involved in the process of translation termination. Nonsense suppression can also result from an aa-tRNA that decodes a termination codon (suppressor tRNA) in this case only one of the termination codons is efficiently suppressed (Hawthorne and Leupold 1974 Stansfield and Tuite 1994). 

The eukaiyotic translation termination factors eRFl and eRF3... 

In eukaryotes, translation termination is mediated by two essential release factors eRFl (in yeast encoded by SUP45) and eRF3 (in yeast encoded by SUP35), which act as class I and II factors respectively (Frolova et al. 1994 Stansfield et al. 1995b Zhouravleva et al. 1995). eRFl and eRF3 interact both in vitro and in vivo and form a heterodimeric complex (Stansfield et al. 1995b Paushkin et al. 1997 Frolova et al. 1998 Ito et al. 1998 Eurwilaichitr et al. 1999). 

Accurate selection of translation termination factors to ribosomes containing a stop codon in the A-site is less well understood. A picture is only beginning to emerge as the bacterial 708 ribosome and class I release factor RF2 atomic models have recently been fitted into cryo-EM stmctures. Via multiple interactions RF2 connects the ribosomal decoding site with the PTC and functionally mimics a tRNA molecule in the A-site. In the complex RF2 is close to helices 18, 44, and 31 of the 168 rRNA, small subunit ribosomal protein 812, helices 69, 71, 89, and 92 of the 238 rRNA, the L7/L12 stalk, and protein LI 1 of the large subunit (Arkov et al. 2000 Klaholz et al. 2003 Rawat et al. 2003). The L7/L12 stalk inter-... 

Components of the translational apparatus and mutations thereof that affect translation termination... 

Mutants in ribosomal RNA that affect the fidelity of translation termination... 

The effect of mutations in eRFl and eRF3 on the efficiency of translation termination in yeast has been extensively studied. A variety of mutations in both translation termination factor subunits results in a nonsense suppression phenotype (Eustice et al. 1986 Song and Liebman 1989 All-Robyn et al. 1990 Wakem and Sherman 1990 Stansfield et al. 1995a, 1997 Bertram et al. 2000 Velichutina et al. 2001 Cosson et al. 2002 Bradley et al. 2003 Chabelskaya et al. 2004 Salas-Marco and Bedwell 2004). 

As illustrated by the [PS / ] phenomenon the relative abundance of the eRFl/eRF3 complexes is an important determinant for the efficiency of translation termination. Similar effects have been obtained in depletion studies and with eRF3 and eRFl mutants that decrease their cellular concentration (Stansfield et al. 1996 Moskalenko et al. 2003 Chabelskaya et al. 2004 Salas-Marco and Bedwell 2004). Wild type yeast contains approximately 10- to 20-fold fewer termination factors compared to ribosomes (Didichenko et al. 1991 Stansfield et al. 1992). The threshold level of eRFl/eRF3 required to maintain viability is even lower. A 10-fold decrease reduces viability by only about 10% (Valouev et al. 2002) and a decrease in eRF3 of 99% does not affect viability of the cells significantly (Chabelskaya et al. 2004). As eRF3 is associated with polysomes or ribosomes, the mechanism of translation termination depends on efficient recycling (Didichenko et al. 1991 and compare below). 

Recent studies have shown that proteins interacting with the release factors can modulate the efficiency of stop codon readthrough. Physical and functional interaction with the translation termination factors was demonstrated for different components of the translational machinery. 

Although the exact mechanism by which Upflp influences translation termination remains unclear the function is connected to the well-documented physical interaction be-... 

Coupling between translation termination and translation initiation... 

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