3.A.18 The Nuclear mRNA Exporter (mRNA-E) Family
In eukaryotic cells, pre-mRNAs are primarily transcribed by RNA polymerase II (RNAPII); this process is followed by complex RNA processing steps that include capping, splicing, and polyadenylation to produce mature mRNAs. Following processing, mRNA is exported as a large mRNA-protein complex (mRNP) through the nuclear pore to the cytoplasm for subsequent translation. Nuclear mRNA export depends on steps preceding and following transport through nuclear pore complexes (Rodríguez-Navarro and Hurt, 2011).
The transport of mRNA from the nucleus to the cytoplasm is linked to pre-mRNA splicing, especially in the metazoans. Exon junction complexes (EJCs), which are deposited on mRNAs at splicing, form the basis of this connection. The EJC consists of four core proteins, eIF4A3, Y14, Magoh, and MLN51, plus other auxiliary proteins including REF, UAP56, RNPS1, SRm160, Pinin, Acinus L, SAP18, and hUpf3. The recruitment of REF during mRNA biogenesis is thought to be responsible for the increased export of spliced mRNA. A DEAD box RNA helicase, UAP56, is required for the recruitment of REF to mRNA. Subsequently, UAP56 is displaced from REF by the mRNA export factor TAP. TAP forms a heterodimer with p15 that then directly interacts with the nuclear pore to facilitate mRNP transport into the cytoplasm. An mRNA export factor, Dbp5, has a C-terminal region that interacts with the ATPase activator Gle1 (Dossani et al., 2009).
Some of the mRNA-E family components are distantly related to the yeast Nuclear mRNA Exporter (TREX) family (3.A.22), the small nuclear RNA Exporter (snRNA-E) family (9.A.60), and the Peroxysomal Protein Importer (PPI) family (3.A.20). Some are also found as constituents of the Nuclear Pore Complex (NPC) family (1.I.1).
The reaction catalyzed by mRNA-E is:
mRNA (nucleus) → mRNA (cytoplasm)
The nuclear mRNA Export Complex (mRNA-E also called TREX) (including the exon junction complex) [TAP+p15 interact as a complex with the nuclear pore to facilitate mRNA transport to the cytoplasm] (Nojimma et al. 2007; Cheng et al., 2006)
The mRNA-E complex of Homo sapiens
Exon junction complex proteins
eIF4A3 (Eukaryotic initiation factor 4A, isoform3; ATP-dep. RNA helicase) (P38919)
RNA binding protein Y14 (8A) (Q9Y5S9)
REF (Nuclear RNA Export Factor) (Q9UBU9)
UAP56 (RNA helicase) (Q13838)
RNPS1 (RNA-binding protein/ser-rich) (Q15287)
SRm160 (ser/arg repetitive matrix protein of 160 kDa) (Q8IYB3)
Pinin (Nuclear protein SDK3) (Q9H307)
Acinus L (Apoptotic Chromatin Condensation inducer) (Q9UKV3)
SAP18 (Sin 3-associated protein, p18 (O00422)
hUpf3 (mRNA decapping protein) (Q9NPI6)
TAP (mRNA export factor) (Q9UBU9)
p15 (Forms a heterodimer with TAP) (P13986)
Nuclear cap binding protein of 80kDa, CBP80 (Q09161)
RNA-binding protein, Aly (Tho4) (Q86V81)
Dbp5 (Son) (P18583)