Journal article
Combined tRNA modification defects impair protein homeostasis and synthesis of the yeast prion protein Rnq1



Publication Details
Authors:
Schaffrath, R.; Klassen, R.
Publisher:
TAYLOR & FRANCIS INC
Publication year:
2017
Journal:
Prion
Pages range:
48-53
Volume number:
11
Issue number:
1
Start page:
48
End page:
53
Number of pages:
6
ISSN:
1933-6896

Abstract
Modified nucleosides in tRNA anticodon loops such as 5-methoxy-carbonyl-methyl-2-thiouridine (mcm(5)s(2)U) and pseuduridine () are thought to be required for an efficient decoding process. In Saccharomyces cerevisiae, the simultaneous presence of mcm(5)s(2)U and 38 in tRNA(UUG)(Gln) was shown to mediate efficient synthesis of the Q/N rich [PIN+] prion forming protein Rnq1.(1) In the absence of these two tRNA modifications, higher than normal levels of hypomodified tRNA(UUG)(Gln), but not its isoacceptor tRNA(CUG)(Gln) can restore Rnq1 synthesis. Moroever, tRNA overexpression rescues pleiotropic phenotypes that associate with loss of mcm(5)s(2)U and 38 formation. Notably, combined absence of different tRNA modifications are shown to induce the formation of protein aggregates which likely mediate severe cytological abnormalities, including cytokinesis and nuclear segregation defects. In support of this, overexpression of the aggregating polyQ protein Htt103Q, but not its non-aggregating variant Htt25Q phenocopies these cytological abnormalities, most pronouncedly in deg1 single mutants lacking 38 alone. It is concluded that slow decoding of particular codons induces defects in protein homeostasis that interfere with key steps in cytokinesis and nuclear segregation.


Keywords
5-methoxycarbonylmethyl-2-thiouridine, [PIN+], pseudouridine, translation, tRNA modification


Authors/Editors

Last updated on 2019-25-07 at 18:59