The DExH/D box protein HEL/UAP56 is essential for mRNA nuclear export in Drosophila

Dbp5 is the only member of the DExH/D box family of RNA helicases that is d irectly implicated in the export of messenger RNAs from the nucleus of yeas t and vertebrate cells [1-3]. Dbp5 localizes in the cytoplasm and at the cy toplasmic face of the nuclear pore complex (NPC) [1-5]. In an attempt to id entify proteins present in a highly enriched NPC fraction, two other helica ses were detected: RNA helicase A (RHA) and UAP56. This suggested a role fo r these proteins in nuclear transport. Contrary to expectation, we show tha t the Drosophila homolog of Dbp5 is not essential for mRNA export in cultur ed Schneider cells. In contrast, depletion of HEL, the Drosophila homolog o f UAP56, inhibits growth and results in a robust accumulation of polyadenyl ated RNAs within the nucleus. Consequently, incorporation of [S-35]methioni ne into newly synthesized proteins is inhibited. This inhibition affects th e expression of both heat-shock and non-heat-shock mRNAs, as well as intron -containing and intronless mRNAs. In HeLa nuclear extracts, UAP56 preferent ially, but not exclusively, associates with spliced mRNAs carrying the exon junction complex (EJC). We conclude that HEL is essential for the export o f bulk mRNA in Drosophila. The association of human UAP56 with spliced mRNA s suggests that this protein might provide a functional link between splici ng and export.