A conserved and essential basic region mediates tRNA binding to the Elp 1 subunit of the S accharomyces cerevisiae Elongator complex
Elongator is a conserved, multi‐protein complex discovered in S accharomyces cerevisiae , loss of which confers a range of pleiotropic phenotypes. Elongator in higher eukaryotes is required for normal growth and development and a mutation in the largest subunit of human Elongator ( Elp 1) causes fam...
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Veröffentlicht in: | Molecular microbiology 2014-06, Vol.92 (6), p.1227-1242 |
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Format: | Artikel |
Sprache: | eng |
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Zusammenfassung: | Elongator is a conserved, multi‐protein complex discovered in
S
accharomyces cerevisiae
, loss of which confers a range of pleiotropic phenotypes. Elongator in higher eukaryotes is required for normal growth and development and a mutation in the largest subunit of human Elongator (
Elp
1) causes familial dysautonomia, a severe recessive neuropathy. Elongator promotes addition of mcm
5
and ncm
5
modifications to uridine in the
tRNA
anticodon ‘wobble’ position in both yeast and higher eukaryotes. Since these modifications are required for the
tRNAs
to function efficiently, a translation defect caused by hypomodified
tRNAs
may therefore underlie the variety of phenotypes associated with Elongator dysfunction. The
Elp
1 carboxy‐terminal domain contains a highly conserved arginine/lysine‐rich region that resembles a nuclear localization sequence (
NLS
). Using alanine substitution mutagenesis, we show that this region is essential for Elongator's function in
tRNA
wobble uridine modification. However, rather than acting to determine the nucleo‐cytoplasmic distribution of Elongator, we find that the basic region plays a critical role in a novel interaction between
tRNA
and the
Elp
1 carboxy‐terminal domain. Thus the conserved basic region in
Elp
1 may be essential for
tRNA
wobble uridine modification by acting as
tRNA
binding motif. |
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ISSN: | 0950-382X 1365-2958 |
DOI: | 10.1111/mmi.12624 |