Sökning: WFRF:(Mahmud A. K. M. Firoj)
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Loss of ncm5 and mc...
Loss of ncm5 and mcm5 wobble uridine side chains results in an altered metabolic profile
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- Karlsborn, Tony, 1987- (författare)
- Umeå universitet,Institutionen för molekylärbiologi (Teknisk-naturvetenskaplig fakultet),Anders Byström
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- Mahmud, A K M Firoj (författare)
- Umeå universitet,Institutionen för molekylärbiologi (Teknisk-naturvetenskaplig fakultet),Maria Fällman
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- Tükenmez, Hasan, 1987- (författare)
- Umeå universitet,Institutionen för molekylärbiologi (Teknisk-naturvetenskaplig fakultet),Anders Byström
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- Byström, Anders S. (författare)
- Umeå universitet,Institutionen för molekylärbiologi (Teknisk-naturvetenskaplig fakultet),Anders Byström
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(creator_code:org_t)
- 2016-09-27
- 2016
- Engelska.
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Ingår i: Metabolomics. - : Springer. - 1573-3882 .- 1573-3890. ; 12:12
- Relaterad länk:
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https://doi.org/10.1...
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https://urn.kb.se/re...
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https://doi.org/10.1...
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Abstract
Ämnesord
Stäng
- 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.
Ämnesord
- 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)
Nyckelord
- Elongator complex
- tRNA wobble uridine modifications
- Translation
- ELP3
- Metabolomics
- Metabolic profiling
- molekylärbiologi
- Molecular Biology
Publikations- och innehållstyp
- ref (ämneskategori)
- art (ämneskategori)
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