Skip to content
Login Register

#mRNA export

2 public questions tagged with this topic.

Protein Sorting and Trafficking

Which of the following proteins is not required for nuclear export of mRNA?

Nuclear export of mature messenger ribonucleoproteins employs dedicated adaptors that recognize RNA processing marks rather than leucine-rich export signals. After splicing, exon junction complex and cap binding complex recruit TREX components including THO complex, UAP56 helicase and Aly/REF adaptor coating 5' region of transcript and providing platform for NXF1-NXT1 heterodimer, called TAP-p15 in metazoans, that binds via arginine-rich domains and directly engages FG nucleoporins through its NTF2-like and UBA domains for translocation. On cytoplasmic face, DDX19/Dbp5 helicase anchored by Nup214 interacts with Gle1 and inositol hexakisphosphate to stimulate ATP hydrolysis, displacing NXF1, Aly and other nuclear proteins, ensuring unidirectional release and immediate engagement with translation initiation factors. Ran-GTP essential for CRM1-mediated protein export is dispensable; leptomycin B that blocks CRM1 or Ran mutants leave bulk poly(A) export unaffected. While ATPase activity of Dbp5 is absolutely required for remodeling, generic ATPase not part of this pore-associated complex is unnecessary, so distinguishing specific Dbp5-dependent ATPase versus unrelated ATPase clarifies why mRNA export bypasses Ran system for continuous gene expression and surveillance.

Ref: Köhler & Hurt, Nature Rev Mol Cell Biol 8: 2007, NXF1-NXT1 and Dbp5 in mRNA Export, Ran Independence.

View Details
Protein Sorting and Trafficking

Which of the following is NOT involved in Ran-independent nuclear export of mRNA?

Export of bulk messenger ribonucleoproteins uses machinery fundamentally separate from Ran-dependent protein and small RNA transport. After capping, splicing and polyadenylation, nascent mRNPs acquire TREX complex including THO subcomplex, DEAD-box helicase UAP56 and adaptors Aly/REF and Thp1 that coat transcript and provide binding platform for export receptor. Heterodimer NXF1-NXT1, called TAP-p15 in metazoans, directly contacts FG repeats of central nucleoporins via its NTF2-like and UBA domains to drive translocation without karyopherins or Ran gradient. Directionality and release do not involve Ran but ATP hydrolysis. On cytoplasmic filaments, DEAD-box helicase Dbp5, known as DDX19 in humans, activated by Gle1 bound to inositol hexakisphosphate, hydrolyzes ATP to remove NXF1, Aly and other nuclear factors, remodeling particle and preventing back-sliding into nucleus. Importin-beta, essential for classical NLS import and leucine-rich export, is not part of this complex. Therefore inhibition of Ran cycle or leptomycin B blockade of CRM1 leaves bulk poly(A) export largely unaffected, while NXF1 depletion arrests mRNA export, illustrating Ran independence of messenger pathway central to gene expression and surveillance of spliced transcripts.

Ref: Stewart M, Science 318: 2007, Nuclear Export of mRNA via NXF1-NXT1 and Dbp5 Helicase.

View Details