Toompuu Marina, Kärblane Kairi, Pata Pille, Truve Erkki, Sarmiento Cecilia
a Department of Gene Technology , Tallinn University of Technology , Tallinn , Estonia.
Cell Cycle. 2016 May 2;15(9):1234-47. doi: 10.1080/15384101.2016.1160972. Epub 2016 Mar 17.
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.
ABCE1是一种高度保守的蛋白质，普遍存在于真核生物和古细菌中，对不同生物体的生存能力至关重要。ABCE1最初被鉴定为核糖核酸酶L抑制剂，目前被认为是一种参与真核生物翻译和核糖体生物发生多个阶段的必需翻译因子。然而，ABCE1重要功能的本质仍未得到解释。在此，我们研究ABCE1在人类细胞增殖中的作用及其与翻译的可能联系。我们发现，通过小干扰RNA（siRNA）耗尽ABCE1会导致细胞生长速率降低，原因是细胞在S期积累，同时伴有DNA合成效率低下以及组蛋白mRNA和蛋白质水平降低。我们推断，除了在一般翻译中的作用外，ABCE1还参与组蛋白生物合成和DNA复制，因此对正常的S期进程至关重要。此外，我们分析了ABCE1是否通过与已知控制细胞增殖相关蛋白质合成的真核起始因子3（eIF3）复合物亚基结合而参与转录本特异性翻译。然而，一些受eIF3A调控的此类靶标的表达水平并未因ABCE1的耗尽而受到一致影响。
