Biology Reference
In-Depth Information
Fig. 2
Nuclear mRNA export pathways. Shown is a schematic overview of several nuclear
mRNA export pathways used by retroviruses or by metazoan cells. Retroviral nuclear RNA
export: unspliced mRNAs encoded by the simple retrovirus MPMV are exported via direct bind-
ing of the constitutive transport element (
CTE
) RNA target to the cellular mRNA export receptor
TAP-p15; unspliced RNA encoded by HIV-1 binds via the Rev-responsive element (
RRE
) RNA
target to the viral factor Rev. Rev then interacts with the cellular protein CRM1 through its
leucine-rich NES, thus mediating nuclear export of unspliced HIV-1 mRNA. Metazoan nuclear
RNA export: ribosomal RNAs, small nuclear RNAs (
U snRNAs
) as well as some specific mRNAs
are exported from the nucleus via the karyopherin CRM1; however, adaptor proteins binding to
CRM1 via a leucine-rich NES are required to mediate these interactions. Bulk cellular mRNA
export occurs via the TAP-p15 export receptor: during splicing of vertebrate mRNA, a complex of
proteins, the exon junction complex (
EJC
) that contains UAP56 and REF is deposited on spliced
mRNAs upstream of exon-exon junctions. REF proteins present in EJCs subsequently recruit the
export receptor TAP-p15. Association of TAP-p15 with the mRNPs displaces UAP56
of introns and addition of the 3′ poly(A) tail (Bentley 2002; Maniatis and Reed
2002). The removal of introns results in the deposition of a protein complex, termed
exon junction complex (EJC), on the RNA molecule immediately upstream of the
splice site (Le Hir et al. 2000). One of the components of the EJC is the DExD/H
box protein UAP56 (named Sub2p in
Saccharomyces cerevisiae
), a putative RNA
helicase, which is thought to couple mRNA splicing with nuclear export (Reed and
Hurt 2002). As a next step, UAP56 recruits the adapter protein Aly/REF (Yra1p in
S. cerevisiae
) to the mRNA, and Aly/REF subsequently interacts with the het-
erodimeric TAP-p15, leading to the efficient export of the mRNA through the
nuclear pore complex (Luo et al. 2001; Strasser and Hurt 2001) (Fig. 2). Interestingly,
Sub2p is required for nuclear export of both intron-containing as well as intronless
mRNAs, suggesting that the association of the helicase with the mRNA molecule is
