A novel type of + 1 frameshift suppressor: a base substitution in the anticodon stem of a yeast mitochondrial serine-tRNA causes frameshift suppression.

Abstract

We have identified a spontaneous mitochondrial mutation, mfs‐1 (mitochondrial frameshift suppressor‐1), which suppresses a + 1 frameshift mutation localized in the yeast mitochondrial oxi1 gene. The suppressor strain exhibits a single base change (C to U) at position 42 of the mitochondrial serine‐tRNA (UCN). To our knowledge, this is the first reported case showing that a mutation in the anticodon stem of a tRNA can cause frameshift suppression. The expression and aminoacylation of the mutant tRNASer(UCN) are not significantly affected. However, the base change at position 42 has two effects: first, residue U27 of the mutant tRNA is not modified to pseudouridine as observed in wild‐type tRNASer(UCN). Second, the base change and/or the lack of modification of U27 leads to an alteration in the secondary/tertiary structure of the mutant tRNA. It is possible that there are such structural changes in the anticodon loop that enable the tRNA to read a four base codon, UCCA, thus restoring the wild‐type reading frame.

Lack of Pseudouridine 38/39 in the Anticodon Arm of Yeast Cytoplasmic tRNA Decreases in Vivo Recoding Efficiency

“…The same conclusion can be reached for the lack of m 5 C at position 48 in the variable loop of tRNA UAG Leu , m 5 C at position 49 at the T-stem of tRNA GCC Gly , or the absence of ⌿27 in tRNA UAG Leu and probably also in tRNA CCU Arg (this mature tRNA has not been sequenced so far). Notably, a ϩ1 frameshift suppressor tRNA UGA Ser has been identified in yeast mitochondria (65). This mutant bears a C to U base change at position 42, thus leading to a G°U wobble at base pair 28 -42 of the anticodon helix.…”

“…Pus1p catalyzes the formation of ⌿ at positions 26,27,28,34,35,36,65, and 67 in cytoplasmic tRNA (14) as well as position 44 in U2 small nuclear RNA (15). Pus3p, Pus4p, and Pus6p act at positions 38, 39 (16), 55 (17), and 31 (18), respectively, in both cytoplasmic and mitochondrial tRNAs (Fig.…”

Chloroplast heteroplasmicity is stabilized by an amber-suppressor tryptophan tRNA(CUA).

“…To our knowledge, there has been only one previous report of an organellar tRNA suppressor mutation (37). In that case, an apparently homoplasmic anticodon-stem mutation of mitochondrial tRNAscr was found to suppress a + 1 frameshift mutation within the S. cerevisiae oxil gene (37,38).…”

“…In that case, an apparently homoplasmic anticodon-stem mutation of mitochondrial tRNAscr was found to suppress a + 1 frameshift mutation within the S. cerevisiae oxil gene (37,38). Whereas it is difficult to study organellar mutations in multicellular organisms, it is intriguing that common tRNA suppressors have been lacking from the organelle genetics of S. cerevisiae and C. reinhardtii.…”

The Salmonella typhimurium uracil-sensitive mutation use is in argU and encodes a minor arginine tRNA

“…Several speculative proposals have been advanced to explain the pleiotropic nature of both mutants (9,17), but none of these proposals have been confirmed. Interestingly, there is only one other report of a mutation in the anticodon stem of a tRNA (10). In this case, the substitution of C-42 by U-42 in the anticodon stem of the mitochondrial serinetRNA (UCN) causes this tRNA to be a +1 frameshift suppressor.…”