The essential vertebrate ABCE1 protein interacts with eukaryotic initiation factors.
The ABCE1 gene is a member of the ATP-binding cassette (ABC) multigene family and is composed of two nucleotide binding domains and an N-terminal Fe-S binding domain. The ABCE1 gene encodes a protein originally identified for its inhibition of ribonuclease L, a nuclease induced by interferon in mammalian cells. The protein is also required for the assembly of the HIV and SIV gag polypeptides. However, ABCE1 is one of the most highly conserved proteins and is found in one or two copies in all characterized eukaryotes and archaea. Yeast ABCE1/RLI1 is essential to cell division and interacts with translation initiation factors in the assembly of the pre-initiation complex. We show here that the human ABCE1 protein is essential for in vitro and in vivo translation of mRNA and that it binds to eIF2alpha and eIF5. Inhibition of the Xenopus ABCE1 arrests growth at the gastrula stage of development, consistent with a block in translation. The human ABCE1 gene contains 16 introns, and the extremely high degree of amino acid identity allows the evolution of its introns to be examined throughout eukaryotes. The demonstration that ABCE1 plays a role in vertebrate translation initiation extends the known functions of this highly conserved protein. Translation is a highly regulated process important to development and pathologies such as cancer, making ABCE1 a potential target for therapeutics. The evolutionary analysis supports a model in which an ancestral eukaryote had large number of introns and that many of these introns were lost in non-vertebrate lineages.
Chen
Zhang-Qun
ZQ
Basic Research Program, SAIC-Frederick Inc., National Cancer Institute, National Institutes of Health, Frederick, MD 21702, USA.
Dong
Jinsheng
J
Ishimura
Akihiko
A
Daar
Ira
I
Hinnebusch
Alan G
AG
Dean
Michael
M
D018528:ATP-Binding Cassette Transporters / Q000378:metabolism / Q000502:physiology*; D000111:Acetylcysteine / Q000378:metabolism; D000595:Amino Acid Sequence; D000818:Animals; D002455:Cell Division; D002460:Cell Line; D018833:Chaperonins / Q000378:metabolism / Q000502:physiology*; D015852:Eukaryotic Initiation Factor-2 / Q000378:metabolism; D039642:Eukaryotic Initiation Factors / Q000737:chemistry; D019143:Evolution, Molecular; D006678:HIV / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D015151:Immunoblotting; D007372:Interferons / Q000378:metabolism; D007438:Introns; D008969:Molecular Sequence Data; D005810:Multigene Family; D010448:Peptide Initiation Factors / Q000737:chemistry / Q000378:metabolism; D011132:Polyribosomes / Q000378:metabolism; D014176:Protein Biosynthesis; D017434:Protein Structure, Tertiary; D012333:RNA, Messenger / Q000378:metabolism; D034741:RNA, Small Interfering / Q000378:metabolism; D016601:RNA-Binding Proteins / Q000378:metabolism; D012260:Ribonucleases / Q000737:chemistry; D017386:Sequence Homology, Amino Acid; D015302:Simian Immunodeficiency Virus; D014981:Xenopus; D014982:Xenopus laevis; D000097574:Eukaryotic Translation Initiation Factor 5A
D018528:ATP-Binding Cassette Transporters; D000111:Acetylcysteine; D018833:Chaperonins; D015852:Eukaryotic Initiation Factor-2; D039642:Eukaryotic Initiation Factors; D007372:Interferons; D010448:Peptide Initiation Factors; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D016601:RNA-Binding Proteins; D012260:Ribonucleases; D000097574:Eukaryotic Translation Initiation Factor 5A; C501917:ABCE1 protein, human