The bornavirus-derived human protein EBLN1 promotes efficient cell cycle transit, microtubule organisation and genome stability

Abstract

It was recently discovered that vertebrate genomes contain multiple endogenised nucleotide sequences derived from the non-retroviral RNA bornavirus. Strikingly, some of these elements have been evolutionary maintained as open reading frames in host genomes for over 40 million years, suggesting that some endogenised bornavirus-derived elements (EBL) might encode functional proteins. EBLN1 is one such element established through endogenisation of the bornavirus N gene (BDV N). Here, we functionally characterise human EBLN1 as a novel regulator of genome stability. Cells depleted of human EBLN1 accumulate DNA damage both under non-stressed conditions and following exogenously induced DNA damage. EBLN1-depleted cells also exhibit cell cycle abnormalities and defects in microtubule organisation as well as premature centrosome splitting, which we attribute in part, to improper localisation of the nuclear envelope protein TPR. Our data therefore reveal that human EBLN1 possesses important cellular functions within human cells, and suggest that other EBLs present within vertebrate genomes may also possess important cellular functions.

Interactions among eukaryotes, retrotransposons and riboviruses: endogenous riboviral elements in eukaryotic genomes

“…Surprisingly, ribovirus-derived DNA is not just a byproduct of chance interactions between riboviruses and retrotransposons: at least in insects, these interactions play important roles in antiviral immunity (Goic et al, 2013(Goic et al, , 2016Tassetto et al, 2017;Poirier et al, 2018). Additionally, some ribovirus-derived EVEs also play roles in their hosts (Fujino et al, 2014;Myers et al, 2016). These fi ndings provide support for a novel concept regarding biological interactions among riboviruses, retrotransposons and eukaryotic genomes.…”

“…Although the presence of ORFs does not always mean that they encode proteins, such observations suggest that it is likely that these EVEs encode proteins in their hosts. Indeed, several riboviral EVEs have been shown to express proteins (Fujino et al, 2014;Kobayashi et al, 2016;Myers et al, 2016;Horie, 2017). Below, I summarize known and possible protein-encoding riboviral EVEs in animals.…”

“…Here, I will briefly consider the known and possible functions of bornavirus-derived EVEs (endogenous bornavirus-like elements, EBLs), which have been well described in several review papers (Honda and Tomonaga, 2016;Horie, 2017). Some EBLs were shown to express protein products in mammals, such as humans, ground squirrels and elephants (Ewing et al, 2007;Fujino et al, 2014;Kobayashi et al, 2016;Myers et al, 2016). Some of these seem to be functional in the cells: an EBL in humans is apparently involved in the regulation of genome stability (Myers et al, 2016), and another in thirteen-lined ground squirrels may function as an anti-bornaviral gene (Fujino et al, 2014).…”

“…Some EBLs were shown to express protein products in mammals, such as humans, ground squirrels and elephants (Ewing et al, 2007;Fujino et al, 2014;Kobayashi et al, 2016;Myers et al, 2016). Some of these seem to be functional in the cells: an EBL in humans is apparently involved in the regulation of genome stability (Myers et al, 2016), and another in thirteen-lined ground squirrels may function as an anti-bornaviral gene (Fujino et al, 2014). Several EBLs in bats of the genus Eptesicus and afrotherian animals (e.g., elephant) have also been strongly suggested to encode functional proteins, although their functions remain unclear (Horie et al, 2016;Kobayashi et al, 2016).…”

Influence of Endogenous Viral Sequences on Gene Expression

“…Indeed, some studies have reported that hsEBLN-1 proteins were detected in particular cell lines [63]. Moreover, Kobayashi et al reported that EBLNs encode functional proteins in afrotherians [10].…”