RNA Export through the NPC in Eukaryotes

Abstract

In eukaryotic cells, RNAs are transcribed in the nucleus and exported to the cytoplasm through the nuclear pore complex. The RNA molecules that are exported from the nucleus into the cytoplasm include messenger RNAs (mRNAs), ribosomal RNAs (rRNAs), transfer RNAs (tRNAs), small nuclear RNAs (snRNAs), micro RNAs (miRNAs), and viral mRNAs. Each RNA is transported by a specific nuclear export receptor. It is believed that most of the mRNAs are exported by Nxf1 (Mex67 in yeast), whereas rRNAs, snRNAs, and a certain subset of mRNAs are exported in a Crm1/Xpo1-dependent manner. tRNAs and miRNAs are exported by Xpot and Xpo5. However, multiple export receptors are involved in the export of some RNAs, such as 60S ribosomal subunit. In addition to these export receptors, some adapter proteins are required to export RNAs. The RNA export system of eukaryotic cells is also used by several types of RNA virus that depend on the machineries of the host cell in the nucleus for replication of their genome, therefore this review describes the RNA export system of two representative viruses. We also discuss the NPC anchoring-dependent mRNA export factors that directly recruit specific genes to the NPC.

Figure 1

The major routes of RNA export. The transcripts undergo processing and associate with export receptors. This figure shows the representative export receptors for each RNA. CBC: cap-binding complex.

Figure 2

Nxf1-dependent mRNA export. Nascent pre-mRNA is spliced by the spliceosome, and then AlyRef, Uap56, and THO assemble into TREX-1. Uap56 can bind pre-mRNA independently of THO and AlyRef, but it is unclear whether the Uap56 that docks to TREX-1 is distinct from the Uap56 that binds pre-mRNA before binding to TREX-1; i.e., model (i) versus model (ii). Spliced mRNA within TREX-1 recruits a NXf1-Nxt1 heterodimer that allows the mRNA to traverse the nuclear pore complex (NPC). INM: inner nuclear membrane, ONM: outer nuclear membrane.

Figure 3

Crm1-dependent mRNA export. Several subsets of mRNA are exported by Crm1. There are four known pathways: (i) HuR-mediated; (ii) LRPPRC-mediated; (iii) Nxf3-mediated; and (iv) U snRNA export. Each pathway requires binding of Crm1 and RanGTP. Hydrolysis of GTP by RanGAP on the cytoplasmic face of the NPC releases mRNA into the cytoplasm.

Figure 4

Transportation of tRNA. Nascent tRNA is exported to the cytoplasm and processed into mature tRNA, which remains in the cytoplasm and can function in protein synthesis. However, a tRNA retrograde import pathway operates under some stress conditions. There are several known tRNA export receptors in yeast (Los1, Ssa2, and Mtr10), and Xpot has been identified in humans.

Figure 5

MicroRNA export pathways. Nascent miRNA is processed in both the nucleus and the cytoplasm. The nuclear export receptor involved in the Dicer-independent pathway is unknown.

Figure 6

(i) Structure of the HIV-1 genome. The genome of HIV-1 encodes 15 proteins and a genomic RNA, which are all derived from a single transcript; (ii) The components of three polyproteins, Gag, Pol, and Env; (iii) mRNA export in HIV-1. In the early phase, transcripts of HIV-1 are exported into the cytoplasm in a splicing-dependent manner. mRNAs exported in this way encode proteins including Rev. Rev protein is localized in the nucleus, where it is bound to RRE, which is present in an intron. The nuclear export receptor Crm1 is recruited to Rev. As a result, intron-containing mRNAs are exported to the cytoplasm.