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Exporting RNA from the nucleus to the cytoplasm

Nature Reviews Molecular Cell Biology volume 8, pages 761–773 (2007)Cite this article

Key Points

  • During eukaryotic gene expression, different classes of RNA molecules are synthesized in the nucleus and are exported to the cytoplasm by mobile export receptors.

  • Export of tRNA requires a specific export receptor called exportin-t, a member of the RanGTP-dependent karyopherin superfamily.

  • Export of microRNA (miRNA) by exportin-5 is coupled to RNA processing by Drosha and Dicer.

  • Small nuclear (sn)RNA export depends on the cap-binding complex (CBC), the general export receptor CRM1 and PHAX, an adaptor with activity that is regulated by phosphorylation.

  • Export of mRNA by the conserved Mex67–Mtr2 receptor depends on various adaptor proteins and is extensively coupled to splicing (in metazoa) or transcription (in yeast). During gene expression, genes can become targeted to the nuclear pore complex (NPC), which could facilitate transcription and mRNA export to the cytoplasm.

  • Export of ribosomal (r)RNA is unique as it depends on several different export receptors that simultaneously bind the large pre-ribosomal subunits, thereby facilitating their passage through the NPC.

Abstract

The transport of RNA molecules from the nucleus to the cytoplasm is fundamental for gene expression. The different RNA species that are produced in the nucleus are exported through the nuclear pore complexes via mobile export receptors. Small RNAs (such as tRNAs and microRNAs) follow relatively simple export routes by binding directly to export receptors. Large RNAs (such as ribosomal RNAs and mRNAs) assemble into complicated ribonucleoprotein (RNP) particles and recruit their exporters via class-specific adaptor proteins. Export of mRNAs is unique as it is extensively coupled to transcription (in yeast) and splicing (in metazoa). Understanding the mechanisms that connect RNP formation with export is a major challenge in the field.

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Figure 1: The different RNA export pathways.
Figure 2: Nuclear export of tRNA and microRNA.
Figure 3: Transcription-coupled or splicing-coupled mRNA export.
Figure 4: Gene gating and mRNA export.
Figure 5: Nuclear export of ribosomal subunits.

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Acknowledgements

We would like to acknowledge critical reading of the manuscript by the members of the Hurt laboratory and by S. Hauf.

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Authors and Affiliations

  1. Biochemie-Zentrum der Universität Heidelberg, Im Neuenheimer Feld 328, Heidelberg, 69120, Germany

    Alwin Köhler & Ed Hurt

  2. Universitätskinderklinik Heidelberg, Im Neuenheimer Feld 151, Heidelberg, 69120, Germany

    Alwin Köhler

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Components involved in RNA export (PDF 162 kb)

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Glossary

Signal recognition particle 7S RNA

The signal recognition particle is an evolutionarily conserved RNA–protein complex that contains a 7S RNA species and targets integral membrane and secretory proteins to the translocation machinery of the endoplasmic reticulum.

5′ cap

A structure at the 5′ end of eukaryotic mRNAs that consists of the m7GpppN cap (in which m7G represents 7-methylguanylate and ppp represents an unusual 5′→5′ triphosphate linkage from m7G to N, which is the first regular nucleotide of the mRNA).

P bodies

(Processing bodies). Discrete cytoplasmic foci that are sites of degradation and surveillance of mRNAs and RNA-mediated gene silencing.

Short hairpin RNA

Artificially generated, usually vector-encoded, RNA that resembles pre-miRNA in structure and is used to experimentally induce RNA interference.

Small interfering RNA

(siRNA). Short double-stranded RNA fragment of ∼22 nucleotides that is derived from longer double-stranded short hairpin RNA. siRNAs guide silencing complexes to their targets by base pairing with specific mRNA sequences.

Survival of motor neurons (SMN) complex

A large multiprotein complex that brings together the Sm proteins and small nuclear RNAs, thereby facilitating small nuclear ribonucleoprotein assembly.

Sm proteins

A set of seven proteins that are arranged as a ring structure on a specific small nuclear RNA-binding site to become part of spliceosomal small nuclear ribonucleoproteins.

AU-rich element

A motif that is located in the 3′-untranslated region of some mRNAs and that can induce rapid mRNA decay.

SR (Ser/Arg-rich) proteins

An abundant class of proteins that are involved in various aspects of mRNA metabolism. They contain one or two RNA-recognition motifs and an Arg/Ser-rich domain that can be phosphorylated at multiple positions.

Exon-junction complex

(EJC). A complex of proteins that is deposited onto mRNA during pre-mRNA splicing (∼20–24 nucleotides upstream of exon–exon junctions). The EJC remains bound to the mRNA during nuclear export and influences surveillance, translation and localization of mature mRNAs in the cytoplasm.

Nonsense-mediated mRNA decay

(NMD). A process by which a cell destroys mRNAs for which translation has been prematurely terminated owing to the presence of a nonsense codon in the coding region.

Inositol hexakisphosphate

(InsP6). One of many small messenger phosphoinositides that is found in cells. InsP6 is synthesized by IPK1 from inositol 1,4,5-trisphosphate (InsP3), a precursor that also regulates the release of intracellular calcium.

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Köhler, A., Hurt, E. Exporting RNA from the nucleus to the cytoplasm. Nat Rev Mol Cell Biol 8, 761–773 (2007). https://doi.org/10.1038/nrm2255

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