Translational control: recognition of the methylated 5' end and an internal sequence in eukaryotic mRNA by the initiation factor that binds methionyl-tRNAfMet.

Proceedings of the National Academy of Sciences of the United States of America ·Vol. 75 ·No. 2 ·1978-02-00 ·Pages 650-4

Kaempfer R, Rosen H, Israeli R

Abstract

Structural analogs of the methylated 5' end (cap) of eukaryotic mRNA, such as 7-methylguanosine 5'-monophosphate, specifically inhibit both GTP-dependent binding of Met-tRNAfMet and binding of globin mRNA to eukaryotic initiation factor 2 (eIF-2). Addition of purified eIF-2 effectively relieves the cap analog-induced inhibition of globin mRNA translation. The analog competitively inhibits the function of eIF-2 and of mRNA in protein synthesis. Binding to eIF-2 of capped mRNA as well as noncapped mRNA, such as Mengo virus RNA, can be inhibited completely by free cap molecules, but much more cap is needed to inhibit binding of Mengo virus RNA. mRNA, whether or not it is capped, competitively inhibits the binding of Met-tRNAfMet to eIF-2. These results provide compelling evidence that eIF-2 recognizes mRNA. It is shown that binding of mRNA to eIF-2 is primarily at an internal sequence, and secondarily through the cap. A model for the function of eIF-2 is presented that can account for all these properties. This model can provide a molecular basis for the differential translation of mRNA species, whether or not they are capped.

MeSH Terms

Eukaryotic Cells Globins/biosynthesis Guanosine Triphosphate/metabolism Methionine Methylation Models, Biological Peptide Initiation Factors Protein Biosynthesis RNA, Messenger/metabolism RNA, Transfer/metabolism RNA, Viral/metabolism Ribosomes/metabolism

Chemicals

Peptide Initiation Factors RNA, Messenger RNA, Viral Guanosine Triphosphate Globins RNA, Transfer Methionine

Authors & Affiliations

3 authors, click to expand affiliations / ORCID

Kaempfer R

Rosen H

Israeli R

References (27)

27 references, click to expand

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Article Info

Journal

Proceedings of the National Academy of Sciences of the United States of America

Abbr.

Proc Natl Acad Sci U S A

ISSN

0027-8424

DOI

10.1073/pnas.75.2.650

Published

1978-02-00

Pages

650-4

Language

English

Region

United States

NLM ID

7505876

PMCID

PMC411313

Subset

External Links

PubMed source DOI: 10.1073/pnas.75.2.650 PMC Full Text View journal details

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Translational control: recognition of the methylated 5' end and an internal sequence in eukaryotic mRNA by the initiation factor that binds methionyl-tRNAfMet.

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