Abstract
We report the cloning and characterization of a DNA damage-inducible (DDI) transcript DDI A121. The full-length human DDI A121 cDNA contains an open reading frame of 113 amino acids, corresponding to a protein of 12.7 kDa. The deduced amino acid sequence of A121 shows high homology to the yeast translation initiation factor (eIF) sui1 and also exhibits perfect identity to the partial sequence of recently purified human eIF1. Expression of human A121 corrected the mutant sui1 phenotype in yeast, demonstrating that human A121 encodes a bona fide translation initiation factor that is equivalent to yeast sui1p. The mammalian A121/SUI1 gene exhibits two transcripts (1.35 kilobases and 0.65 kilobases) containing a common coding region but differing in their 3'-untranslated region. The long and short A121/SUI1 mRNAs are differentially regulated by genotoxic and endoplasmic reticulum stress. The genotoxic stress induction of A121/SUI1 mRNA is conserved in both humans and rodents and occurs in a p53-independent manner. Our identification of a stress-inducible cDNA that encodes eIF1 suggests that modulation of translation initiation appears to occur during cellular stress and may represent an important adaptive response to genotoxic as well as endoplasmic reticulum stress.
Highlights
The nucleotide sequence(s) reported in this paper has been submitted to the GenBankTM/EBI Data Bank with accession number(s) AF100737 and F100738
The BLASTX alignment of the predicted protein sequence of the human A121 cDNA with other protein sequences in the data banks revealed that human A121 is homologous to a less well characterized yeast translation initiation factor named sui1 [16]
Our results demonstrated that human A121/SUI1 mRNA was induced by MMS in all the cell lines tested, whereas its induction in response to UV was cell type-specific
Summary
16487–16493, 1999 Printed in U.S.A. Cloning and Characterization of a Human Genotoxic and Endoplasmic Reticulum Stress-inducible cDNA That Encodes Translation Initiation Factor 1(eIF1A121/SUI1)*. In an attempt to identify and clone the genes corresponding to the remaining novel genotoxic stress-inducible transcripts present within the same library, we have recently cloned and characterized a novel genotoxic stress-inducible gene [8] This gene, named A18 heteronuclear ribonucleoprotein (18hnRNP) is regulated by UV and UV-mimetic agents and encodes a putative glycine-rich RNA and DNA-binding protein [8]. We report the cloning and characterization of another human gene that corresponds to one of the previously uncharacterized genotoxic stress-inducible transcripts named A121. The full-length cDNA of human A121 encodes translation eIF1, showing a high homology to the yeast translation initiation factor sui
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