Different subcellular localizations and functions of human ARD1 variants

Abstract

Abstract. ARD1 is present in various species and has several variants derived from alternative splicing of mRNA. Previously, we reported differential biological functions and cellular distributions of mouse ARD1 (mARD1) variants. However, in comparison to mARD1 variants, human ARD1 (hARD1) variants have been rarely studied. In this study, we characterized a hARD1 variant, hARD1 131 and investigated its cellular activities. hARD1 131 mRNA was isolated from HeLa cells and sequenced. Sequence alignment revealed that, compared to hARD1 235 , the most common form of hARD1, the mRNA sequence encoding hARD1 131 possesses an altered reading frame due to a 46-bp deletion. Thus, hARD1131 and hARD1 235 differ in their C-terminal regions with a partially deleted acetyltransferase domain at the C-terminus of hARD1 131. Moreover, hARD1 131 and hARD1 235 showed different subcellular localizations and biological functions. hARD1 131 was mostly localized in the cell nucleus, whereas hARD1 235 was primarily localized in the cytoplasm. In addition, hARD1 235 stimulated cell proliferation by upregulation of cyclin D1, however hARD1 131 had no influence on cyclin D1 expression and cell growth. Because hARD1 235 enhances cell proliferation by its autoacetylation activity, we examined the autoacetylation activity of hARD1 131 and observed that this function was absent in hARD1 131 . These results suggest that human ARD1 variants have different effects on cell prolifer ation, which may result from distinct subcellular localizations and autoacetylation activities.

The biological functions of Naa10 — From amino-terminal acetylation to human disease

“…Recently, an additional putative splice variant, hNaa10 131 (GenBank accession no. BC063377), was identified by Sanger sequencing in a single clone after amplification of Naa10 from HeLa cDNA (Seo et al, 2015). However, this isoform is identical to Naa10 isoform 2, except that the splice acceptor site is shifted by 1 bp, which results in a frameshift in the resulting mRNA and a premature translational stop.…”

Characterization of Lysine Acetyltransferase Activity of Recombinant Human ARD1/NAA10

“…We assume that the stability of hARD1/NAA10 could rely on its binding to other proteins. ARD1/NAA10 predominantly localizes in cell cytosol as a subunit of the stable complex NatA with Naa15p [25,26]. ARD1/NAA10 was recently found to exist independently from the NatA complex in the cytosol and had the ability to perform post-translational acetylation [27].…”

N-α-acetyltransferase 10 (NAA10) in development: the role of NAA10

“…There are three mouse variants (mNaa10 198 , mNaa10 225 , and mNaa10 235 ) and two human variants (hNaa10 131 and hNaa10 235 ). The mNaa10 225 , mNaa10 235 , and hNaa10 235 are the functional isoforms that contain the full N-acetyltransferase domain sequence, and they have been the most extensively studied and characterized among the aforementioned variants 18 – 20 . Additionally, a homologous gene of NAA10 , termed NAA11 , has been identified.…”