A Sub-Element in PRE enhances nuclear export of intronless mRNAs by recruiting the TREX complex via ZC3H18. Nucleic Acids Res

Viral RNA elements that facilitate mRNA export are useful tools for identifying cellular RNA export fac-tors. Here we show that hepatitis B virus post-transcriptional element (PRE) is one such element, and using PRE several new cellular mRNA export factors were identified. We found that PRE dras-tically enhances the cytoplasmic accumulation of cDNA transcripts independent of any viral protein. Systematic deletion analysis revealed the existence of a 116 nt functional Sub-Element of PRE (SEP1). The RNP that forms on the SEP1 RNA was affin-ity purified, in which TREX components as well as several other proteins were identified. TREX com-ponents and the SEP1-associating protein ZC3H18 are required for SEP1-mediated mRNA export. Signif-icantly, ZC3H18 directly binds to the SEP1 RNA, inter-acts with TREX and is required for stable association of TREX with the SEP1-containing mRNA. Require-ments for SEP1-mediated mRNA export are similar to those for splicing-dependent mRNA export. Consis-tent with these similarities, several SEP1-interacting proteins, including ZC3H18, ARS2, Acinus and Brr2, are required for efficient nuclear export of polyA RNAs. Together, our data indicate that SEP1 en-hances mRNA export by recruiting TREX via ZC3H18. The new mRNA export factors that we identified might be involved in cap- and splicing-dependent TREX recruitment to cellular mRNAs