The Upf1 protein in yeast has been implicated in the
modulation of efficient translation termination as well
as in the accelerated turnover of mRNAs containing
premature stop codons, a phenomenon called nonsense-mediated
mRNA decay (NMD). A human homolog of the yeast UPF1,
termed HUpf1/RENT1, has also been identified. The HUpf1
has also been shown to play a role in NMD in mammalian
cells. Comparison of the yeast and human UPF1 proteins
demonstrated that the amino terminal cysteine/histidine-rich
region and the region comprising the domains that define
this protein as a superfamily group I helicase have been
conserved. The yeast Upf1p demonstrates RNA-dependent ATPase
and 5′ → 3′ helicase activities. In this
paper, we report the expression, purification, and characterization
of the activities of the human Upf1 protein. We demonstrate
that human Upf1 protein displays a nucleic-acid-dependent
ATPase activity and a 5′ → 3′ helicase
activity. Furthermore, human Upf1 is an RNA-binding protein
whose RNA-binding activity is modulated by ATP. Taken together,
these results indicate that the activities of the Upf1
protein are conserved across species, reflecting the conservation
of function of this protein throughout evolution.