Nucleoplasmic Nup98 controls gene expression by regulating a DExH/D-box protein

The nucleoporin Nup98 has been linked to the regulation of transcription and RNA metabolism, ^1-3 but the mechanisms by which Nup98 contributes to these processes remains largely undefined. Recently, we uncovered interactions between Nup98 and several DExH/D-box proteins (DBPs), a protein family well-known for modulating gene expression and RNA metabolism. ^4-6 Analysis of Nup98 and one of these DBPs, DHX9, showed that they directly interact, their association is facilitated by RNA, and Nup98 binding stimulates DHX9 ATPase activity. ⁷ Furthermore, these proteins were dependent on one another for their proper association with a subset of gene loci to control transcription and modulate mRNA splicing. ⁷ On the basis of these observations, we proposed that Nup98 functions to regulate DHX9 activity within the nucleoplasm. ⁷ Since Nup98 is associated with several DBPs, regulation of DHX9 by Nup98 may represent a paradigm for understanding how Nup98, and possibly other FG-Nup proteins, could direct the diverse cellular activities of multiple DBPs.