Structural Biochemistry/Nucleic Acid/RNA/mRNA processing and transfer

mRNA processing and transfer surrounds the movement of mRNA from the nucleus to the cytoplasm. After transcription, a process which occurs in the nucleus, mRNA must travel to the cytoplasm, where it can reach the ribosomes. mRNA travels past the nuclear membrane in the form of mRNP (messenger Ribonucleoprotein), a structure in which contains cargo-carrier components. The cargo (mRNA) requires the assistance of carriers (proteins) in order to be transported across the nuclear membrane. This mechanism makes usage of recyclable proteins and imposes directionality.

=At the nuclear membrane= After the mRNP goes through nuclear processing, the mRNP approaches the NPC (Nuclear Pore Complex). Located at this complex is the TREX-2 complex. The TREX-2 complex is comprised of a Sac3 complex containing Sus1, Cdc31 and Thp1. Together, this TREX-2 complex improves the efficiency in which mRNP enters the NPC transport channel, which occurs by promoting active interactions between the TREX-2 complex and that of approaching mRNPs. Located along the NPC nuclear face, the TREX-2 complex becomes a sort of platform in which the necessary interactions between the TREX-2 complex and the mRNP are favorable. The TREX-2 complex serves as an attractive force, which concentrates export-ready mRNPs and helps promote movement through the NPC.

In addition to the Sac3 complex of the TREX-2 complex, a complex known as the SAGA complex is a part of the TREX-2 complex. The SAGA complex, which is attached to the Sac3 complex, is most known to be the location in which active genes are localized. More specifically, the TREX-2 complex localizes the active genes to pores located on the nuclear basket of the NPC transport channel as well as the SAGA complex.

=Disassembly of the mRNP export complex= Once the mRNP clears the NPC complex, the mRNP becomes exposed to the cytoplasmic conditions. Located in the cytoplasm is an essential DEAD-box helicase known as Dbp5. Dbp5 is responsible for the remodeling of the mRNP complex, essentially removing the carrier aspects of the carrier-cargo relationship of the mRNP. The remodeling of the mRNP, an act whose specifics are unknown, releases Nab2 from the Poly(A) tail of the mRNA and Mex67-Mtr2. As a result, the introduction of Dbp5 isolates the mRNA from the mRNP. However, Dbp5 is not always in an active conformation. Dbp5 flow freely between the nuclear and cytoplasmic side, but only affect the mRNP in the cytoplasmic side. This occurs because of the presence of Gle1 and IP6. Gle1 and IP6 are located on the cytoplasmic face of the NPC. Without these two compounds, Dbp5 remains in a dormant state. This occurs because Gle1 enhances the ATPase efficiency of Dbp5 as well as its affinity for RNA. IP6 enhances the attraction between Gle1 and Dbp5. When an activated Dbp5 remodels the mRNP into the mRNA and the carrier aspects, the Nab2 and Mex67-Mtr2 are recycled. In other words, they flow freely from the cytoplasmic side to the nuclear side and are reused in the formation of the mRNP. The usage of Dbp5 as a means of remodeling the mRNP controls the directionality of the transport. Once the mRNP is separated into the mRNA and carriers, the mRNA cannot re-enter the nucleus. The mRNA that is isolated is ready for translation.

=References= Stewart M. "Nuclear export of mRNA". Trends Biochem Sci. 2010 Nov;35(11):609-17. Epub 2010 Aug 16. Review. Accessed 2012 Nov 20.