Loss of ncm5 and mcm5 wobble uridine side chains results in an altered metabolic profile

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Karlsborn, Tony,1987-Umeå universitet,Institutionen för molekylärbiologi (Teknisk-naturvetenskaplig fakultet),Anders Byström (author)

Loss of ncm5 and mcm5 wobble uridine side chains results in an altered metabolic profile

Article/chapterEnglish2016

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2016-09-27
Springer,2016
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LIBRIS-ID:oai:DiVA.org:umu-125635
https://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-125635URI
https://doi.org/10.1007/s11306-016-1120-8DOI

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Language:English
Summary in:English

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Introduction: The Elongator complex, comprising six subunits (Elp1p-Elp6p), is required for formation of 5-carbamoylmethyl (ncm(5)) and 5-methoxycarbonylmethyl (mcm(5)) side chains on wobble uridines in 11 out of 42 tRNA species in Saccharomyces cerevisiae. Loss of these side chains reduces the efficiency of tRNA decoding during translation, resulting in pleiotropic phenotypes. Overexpression of hypomodified tRNA(s2UUU)(Lys); tRNA(s2UUG)(Gln) and tRNA(s2UUC)(Glu), which in wild-type strains are modified with mcm(5)s(2)U, partially suppress phenotypes of an elp3 Delta strain. Objectives: To identify metabolic alterations in an elp3 Delta strain and elucidate whether these metabolic alterations are suppressed by overexpression of hypomodified tRNA(s2UUU)(Lys); tRNA(s2UUG)(Gln) and tRNA(s2UUC)(Glu). Method: Metabolic profiles were obtained using untargeted GC-TOF-MS of a temperature-sensitive elp3 Delta strain carrying either an empty low-copy vector, an empty high-copy vector, a low-copy vector harboring the wild-type ELP3 gene, or a high-copy vector overexpressing tRNA(s2UUU)(Lys); tRNA(s2UUG)(Gln) and tRNA(s2UUC)(Glu). The temperature sensitive elp3 Delta strain derivatives were cultivated at permissive (30 degrees C) or semi-permissive (34 degrees C) growth conditions. Results: Culturing an elp3 Delta strain at 30 or 34 degrees C resulted in altered metabolism of 36 and 46 %, respectively, of all metabolites detected when compared to an elp3D strain carrying the wild-type ELP3 gene. Overexpression of hypomodified tRNA(s2UUU)(Lys); tRNA(s2UUG)(Gln) and tRNA(s2UUC)(Glu) suppressed a subset of the metabolic alterations observed in the elp3 Delta strain. Conclusion: Our results suggest that the presence of ncm(5)- and mcm(5)-side chains on wobble uridines in tRNA are important for metabolic homeostasis.

Subject headings and genre

NATURVETENSKAP Biologi Biokemi och molekylärbiologi hsv//swe
NATURAL SCIENCES Biological Sciences Biochemistry and Molecular Biology hsv//eng
MEDICIN OCH HÄLSOVETENSKAP Klinisk medicin Endokrinologi och diabetes hsv//swe
MEDICAL AND HEALTH SCIENCES Clinical Medicine Endocrinology and Diabetes hsv//eng
Elongator complex
tRNA wobble uridine modifications
Translation
ELP3
Metabolomics
Metabolic profiling
molekylärbiologi
Molecular Biology

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Mahmud, A K M FirojUmeå universitet,Institutionen för molekylärbiologi (Teknisk-naturvetenskaplig fakultet),Maria Fällman(Swepub:umu)aakk0004 (author)
Tükenmez, Hasan,1987-Umeå universitet,Institutionen för molekylärbiologi (Teknisk-naturvetenskaplig fakultet),Anders Byström(Swepub:umu)htak0003 (author)
Byström, Anders S.Umeå universitet,Institutionen för molekylärbiologi (Teknisk-naturvetenskaplig fakultet),Anders Byström(Swepub:umu)anby0001 (author)
Umeå universitetInstitutionen för molekylärbiologi (Teknisk-naturvetenskaplig fakultet) (creator_code:org_t)

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In:Metabolomics: Springer12:121573-38821573-3890

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