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.

Readthrough of stop codons under limiting ABCE1 concentration involves frameshifting and inhibits nonsense-mediated mRNA decay

“…Since NMD is dependent on active translation ( 78 , 79 ), we next examined whether ABCE1 depletion might inhibit NMD indirectly by causing a global translation inhibition. Notably, a previous study has reported that ABCE1 KD in human cells reduces the general translation level ( 80 ). To assess the overall translation activity in control and ABCE1 KD cells, we pulse-chased HeLa cells with puromycin and detected puromycylated nascent polypeptide chains using an antibody against puromycin (Figure 3A ).…”

Ribosome Recycling by ABCE1 Links Lysosomal Function and Iron Homeostasis to 3ʹ UTR-Directed Regulation and Nonsense-Mediated Decay

“…These data support a requirement for Fe-S cluster biogenesis and ABCE1 in NMD. It has been reported that depletion of ABCE1 globally reduces translation (Toompuu et al, 2016). Because of the dependency of NMD on active translation, this could potentially account for impaired decay of nonsense transcripts in ABCE1-deficient cells.…”

Ribosome recycling factor ABCE1 depletion inhibits nonsense-mediated mRNA decay by promoting stop codon readthrough

“…Since NMD is dependent on active translation (Carter et al, 1995;Thermann et al, 1998), we next examined whether ABCE1 depletion might inhibit NMD indirectly by causing a global translation inhibition. Notably, a previous study has reported that ABCE1 KD in human cells reduces the general translation level (Toompuu et al, 2016). To assess the overall translation activity in control and ABCE1 KD cells, we pulse-chased HeLa cells with puromycin and detected puromycylated nascent polypeptide chains using an antibody against puromycin (Fig.…”