Regulation of ribonucleotide reductase M2 expression by the upstream AUGs

Zizheng Dong, Yang Liu, Jian-Ting Zhang

Research output: Contribution to journalArticle

17 Citations (Scopus)

Abstract

Ribonucleotide reductase catalyzes a rate-limiting reaction in DNA synthesis by converting ribonucleotides to deoxyribonucleotides. It consists of two subunits and the small one, M2 (or R2), plays an essential role in regulating the enzyme activity and its expression is finely controlled. Changes in the M2 level influence the dNTP pool and, thus, DNA synthesis and cell proliferation. M2 gene has two promoters which produce two major mRNAs with 5′-untranslated regions (5′-UTRs) of different lengths. In this study, we found that the M2 mRNAs with the short (63 nt) 5′-UTR can be translated with high efficiency whereas the mRNAs with the long (222 nt) one cannot. Examination of the long 5′-UTR revealed four upstream AUGs, which are in the same reading frame as the unique physiological translation initiation codon. Further analysis demonstrated that these upstream AUGs act as negative cis elements for initiation at the downstream translation initiation codon and their inhibitory effect on M2 translation is eIF4G dependent. Based on the findings of this study, we conclude that the expression of M2 is likely regulated by fine tuning the translation from the mRNA with a long 5′-UTR during viral infection and during the DNA replication phase of cell proliferation.

Original languageEnglish
Pages (from-to)2715-2725
Number of pages11
JournalNucleic Acids Research
Volume33
Issue number8
DOIs
StatePublished - 2005

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5' Untranslated Regions
Initiator Codon
Messenger RNA
Cell Proliferation
Deoxyribonucleotides
Ribonucleotides
Ribonucleotide Reductases
Reading Frames
DNA
Protein Biosynthesis
Virus Diseases
DNA Replication
ribonucleotide reductase M2
Enzymes
Genes

ASJC Scopus subject areas

  • Genetics

Cite this

Regulation of ribonucleotide reductase M2 expression by the upstream AUGs. / Dong, Zizheng; Liu, Yang; Zhang, Jian-Ting.

In: Nucleic Acids Research, Vol. 33, No. 8, 2005, p. 2715-2725.

Research output: Contribution to journalArticle

Dong, Zizheng ; Liu, Yang ; Zhang, Jian-Ting. / Regulation of ribonucleotide reductase M2 expression by the upstream AUGs. In: Nucleic Acids Research. 2005 ; Vol. 33, No. 8. pp. 2715-2725.
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