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Nuclear pore complex composition: a new regulator of tissue-specific and developmental functions

Key Points

  • Nuclear pore complexes (NPCs) are aqueous channels that penetrate the nuclear envelope, thereby connecting the nucleus and the cytoplasm. These structures consist of multiple copies of 30 different proteins known as nucleoporins (NUPs).

  • NPCs control most nucleocytoplasmic transport and have a direct role in genome organization and gene expression regulation.

  • NPCs are highly dynamic and plastic structures. Although the scaffold structure is extremely long-lived and of stable composition in non-dividing cells, peripheral NUPs undergo turnover at different rates.

  • The expression levels of several NUPs vary among different cell types and tissues. Changes in the composition of NPCs can regulate cell differentiation and development.

  • The heterogeneity of NPC composition among different cell types indicates that cells use a combination of different NUPs to assemble NPCs with distinct properties and specialized functions.

Abstract

Nuclear pore complexes (NPCs) are multiprotein aqueous channels that penetrate the nuclear envelope connecting the nucleus and the cytoplasm. NPCs consist of multiple copies of roughly 30 different proteins known as nucleoporins (NUPs). Due to their essential role in controlling nucleocytoplasmic transport, NPCs have traditionally been considered as structures of ubiquitous composition. The overall structure of the NPC is indeed conserved in all cells, but new evidence suggests that the protein composition of NPCs varies among cell types and tissues. Moreover, mutations in various nucleoporins result in tissue-specific diseases. These findings point towards a heterogeneity in NPC composition and function. This unexpected heterogeneity suggests that cells use a combination of different nucleoporins to assemble NPCs with distinct properties and specialized functions.

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Figure 1: Structural organization of the nuclear pore complex.
Figure 2: Mechanisms of nuclear transport.
Figure 3: Peripheral heterochromatin is excluded from the NPC.
Figure 4: NPC functions in genome organization and gene expression.
Figure 5: Specialized nuclear pore complexes in nuclear transport and genome organization.

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Acknowledgements

M.A.D. is a Pew Scholar in the Biomedical Sciences, supported by the Pew Charitable Trust. This work was also supported by the award 10SDG2610290 from the American Heart Association. The authors apologize to all colleagues whose work could not be cited owing to space limitations.

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Glossary

WD domains

Short structural motif, 40 amino acids long, that often terminates in a Trp–Asp (WD) dipeptide.

Dosage compensation complex

In Drosophila melanogaster, this ribonucleoprotein complex, also known as male-specific lethal (MSL) complex, consists of at least five proteins and two noncoding RNAs. Dosage compensation occurs in the male single X chromosome, so that transcription activity is doubled compared to that of each female X chromosome.

SAGA–TREX2 complex

(Spt–Ada–Gcn5–acetyltransferase–transcription export complex 2). Multiprotein complex that interacts with the nuclear pore complex to couple gene transcription with mRNA export.

THO–TREX complex

The THO ((Tho2–Hpr1–Mft1–Thp2) complex is present at gene coding regions to promote transcriptional elongation. THO interacts with Sub2 and Yra1 to form the THO–TREX (transcription export complex) complex, which links transcription and mRNA export.

Progenitor cells

Stem cells differentiate into progenitor cells, which are more developmentally committed to a cell line but are still undifferentiated.

Hypomorphic

A type of mutation that causes a partial loss of gene function by either generating an altered gene product with reduced activity or a wild-type gene product that is expressed at a reduced level.

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Raices, M., D'Angelo, M. Nuclear pore complex composition: a new regulator of tissue-specific and developmental functions. Nat Rev Mol Cell Biol 13, 687–699 (2012). https://doi.org/10.1038/nrm3461

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