Journal article
Independent suppression of ribosomal+1 frameshifts by different tRNA anticodon loop modifications



Publication Details
Authors:
Klassen, R.; Bruch, A.; Schaffrath, R.
Publisher:
TAYLOR & FRANCIS INC
Publication year:
2017
Journal:
RNA Biology
Pages range:
1252-1259
Volume number:
14
Issue number:
9
Start page:
1252
End page:
1259
Number of pages:
8
ISSN:
1547-6286

Abstract
Recently, a role for the anticodon wobble uridine modification 5-methoxycarbonylmethyl-2-thiouridine (mcm(5)s(2)U) has been revealed in the suppression of translational +1 frameshifts in Saccharomyces cerevisiae. Loss of either the mcm(5)U or s(2)U parts of the modification elevated +1 frameshift rates and results obtained with reporters involving a tRNA(UUU)(Lys) dependent frameshift site suggested these effects are caused by reduced ribosomal A-site binding of the hypomodified tRNA. Combined loss of mcm(5)U and s(2)U leads to increased ribosome pausing at tRNA(UUU)(Lys) dependent codons and synergistic growth defects but effects on +1 frameshift rates remained undefined to this end. We show in here that simultaneous removal of mcm(5)U and s(2)U results in synergistically increased +1 frameshift rates that are suppressible by extra copies of tRNA(UUU)(Lys). Thus, two distinct chemical modifications of the same wobble base independently contribute to reading frame maintenance, loss of which may cause or contribute to observed growth defects. Since the thiolation pathway is sensitive to moderately elevated temperatures in yeast, we observe a heat-induced increase of +1 frameshift rates in wild type cells that depends on the sulfur transfer protein Urm1. Furthermore, we find that temperature-induced frameshifting is kept in check by the dehydration of N6-threonylcarbamoyladenosine (t(6)A) to its cyclic derivative (ct(6)A) at the anticodon adjacent position 37. Since loss of ct(6)A in elp3 or urm1 mutant cells is detrimental for temperature stress resistance we assume that conversion of t(6)A to ct(6)A serves to limit deleterious effects on translational fidelity caused by hypomodified states of wobble uridine bases.


Keywords
5-methoxycarbonylmethyl-2-thiouridine, cyclic N6-threonylcarbamoyladenosine, translation, translational frameshift, tRNA modification


Authors/Editors

Last updated on 2019-25-07 at 19:12