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The essential Gcd10p–Gcd14p nuclear complex is required for 1-methyladenosine modification and maturation of initiator methionyl-tRNA

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Anderson, James, Phan, Lon, Cuesta, Rafael, Carlson, Bradley A., Pak, Marie, Asano, Katsura, Björk, Glenn R., Tamame, Mercedes, Hinnebusch, Alan G.·1998·Genes & Development

Abstract

Gcd10p and Gcd14p are essential proteins required for the initiation of protein synthesis and translational repression of GCN4 mRNA. The phenotypes of gcd10 mutants were suppressed by high-copy-number IMT genes, encoding initiator methionyl tRNA (tRNA iMet), or LHP1, encoding the yeast homolog of the human La autoantigen. The gcd10-504 mutation led to a reduction in steady-state levels of mature tRNA iMet, attributable to increased turnover rather than decreased synthesis of pre-tRNA iMet. Remarkably, the lethality of a GCD10 deletion was suppressed by high-copy-number IMT4, indicating that its role in expression of mature tRNA iMet is the essential function of Gcd10p. A gcd14-2 mutant also showed reduced amounts of mature tRNA iMet, but in addition, displayed a defect in pre-tRNA iMet processing. Gcd10p and Gcd14p were found to be subunits of a protein complex with prominent nuclear localization, suggesting a direct role in tRNA iMet maturation. The chromatographic behavior of elongator and initiator tRNA Met on a RPC-5 column indicated that both species are altered structurally in gcd10Δ cells, and analysis of base modifications revealed that 1-methyladenosine (m 1 A) is undetectable in gcd10Δ tRNA. Interestingly,gcd10 and gcd14 mutations had no effect on processing or accumulation of elongator tRNA Met, which also contains m 1 A at position 58, suggesting a unique requirement for this base modification in initiator maturation.

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Metadata

Authors
Anderson, J., Phan, L., Cuesta, R., Carlson, B. A., Pak, M., Asano, K., Björk, G. R., Tamame, M., & Hinnebusch, A. G.
Venue
Genes & Development
Published
1998-12-01
Volume
12
Issue
23
Pages
3650-3662
ISSN
  • 0890-9369 (ISSN-L)
  • 1549-5477
OpenAlex
W2113263393
Cited by
281
References
0
Type
posted content
Language
en
Open access
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CoChat. (2026). Citation check: The essential Gcd10p–Gcd14p nuclear complex is required for 1-methyladenosine modification and maturation of initiator methionyl-tRNA. https://app.cochat.ai/papers/10.1101/gad.12.23.3650
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Anderson, J., Phan, L., Cuesta, R., Carlson, B. A., Pak, M., Asano, K., Björk, G. R., Tamame, M., & Hinnebusch, A. G. (1998). The essential Gcd10p–Gcd14p nuclear complex is required for 1-methyladenosine modification and maturation of initiator methionyl-tRNA. Genes & Development. https://doi.org/10.1101/gad.12.23.3650

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