title: ABCE1 is essential for S phase progression in human cells.
abstract: ABCE1 is a highly conserved protein universally present in eukaryotes and archaea, which is crucial for the viability of different organisms. First identified as RNase L inhibitor, ABCE1 is currently recognized as an essential translation factor involved in several stages of eukaryotic translation and ribosome biogenesis. The nature of vital functions of ABCE1, however, remains unexplained. Here, we study the role of ABCE1 in human cell proliferation and its possible connection to translation. We show that ABCE1 depletion by siRNA results in a decreased rate of cell growth due to accumulation of cells in S phase, which is accompanied by inefficient DNA synthesis and reduced histone mRNA and protein levels. We infer that in addition to the role in general translation, ABCE1 is involved in histone biosynthesis and DNA replication and therefore is essential for normal S phase progression. In addition, we analyze whether ABCE1 is implicated in transcript-specific translation via its association with the eIF3 complex subunits known to control the synthesis of cell proliferation-related proteins. The expression levels of a few such targets regulated by eIF3A, however, were not consistently affected by ABCE1 depletion.
authors.affiliation: a Department of Gene Technology , Tallinn University of Technology , Tallinn , Estonia.
authors.forename: Marina
authors.initials: M
authors.lastname: Toompuu
authors.affiliation: a Department of Gene Technology , Tallinn University of Technology , Tallinn , Estonia.
authors.forename: Kairi
authors.initials: K
authors.lastname: Kärblane
authors.affiliation: a Department of Gene Technology , Tallinn University of Technology , Tallinn , Estonia.
authors.forename: Pille
authors.initials: P
authors.lastname: Pata
authors.affiliation: a Department of Gene Technology , Tallinn University of Technology , Tallinn , Estonia.
authors.forename: Erkki
authors.initials: E
authors.lastname: Truve
authors.affiliation: a Department of Gene Technology , Tallinn University of Technology , Tallinn , Estonia.
authors.forename: Cecilia
authors.initials: C
authors.lastname: Sarmiento
mesh_terms: D018528:ATP-Binding Cassette Transporters / Q000378:metabolism*; D018797:Cell Cycle Proteins / Q000378:metabolism; D049109:Cell Proliferation; D004247:DNA / Q000096:biosynthesis; D015536:Down-Regulation; D039621:Eukaryotic Initiation Factor-3; D005786:Gene Expression Regulation; D057809:HEK293 Cells; D006367:HeLa Cells; D006657:Histones / Q000378:metabolism; D006801:Humans; D014176:Protein Biosynthesis; D021122:Protein Subunits / Q000378:metabolism; D034741:RNA, Small Interfering / Q000378:metabolism; D016196:S Phase
chemical_list: C501917:ABCE1 protein, human; D018528:ATP-Binding Cassette Transporters; D018797:Cell Cycle Proteins; C105988:EIF3A protein, human; D039621:Eukaryotic Initiation Factor-3; D006657:Histones; D021122:Protein Subunits; D034741:RNA, Small Interfering; D004247:DNA
keywords: ABCE1; DNA synthesis; S phase; eIF3; histone synthesis; translation