Review: Dynamic Stability of the Interphase Nucleus in Health and Disease (original) (raw)

RNA movement between the nucleus and the cytoplasm

Current Opinion in Genetics & Development, 1997

The past year has seen significant advances in our understanding of the mechanism of RNA movement between the nucleus and the cytoplasm. The emerging view is that proteins bind to and escort RNAs to their proper subcellular location. The discovery of peptide signals that target nuclear export and the identification of novel protein mediators of RNA export are examples of significant recent discoveries.

Nucleocytoplasmic transport: Diffusion channel or phase transition?

Current Biology, 2001

How exactly large molecules translocate through nuclear pores has been mysterious for a long time. Recent kinetic measurements of transport rates through the pore have led to a novel translocation model that elegantly combines selectivity with very high transport rates.

Mechanism of mRNA transport in the nucleus

Proceedings of The National Academy of Sciences, 2005

The mechanism of transport of mRNA-protein (mRNP) complexes from transcription sites to nuclear pores has been the subject of many studies. Using molecular beacons to track single mRNA molecules in living cells, we have characterized the diffusion of mRNP complexes in the nucleus. The mRNP complexes move freely by Brownian diffusion at a rate that assures their dispersion throughout the nucleus before they exit into the cytoplasm, even when the transcription site is located near the nuclear periphery. The diffusion of mRNP complexes is restricted to the extranucleolar, interchromatin spaces. When mRNP complexes wander into dense chromatin, they tend to become stalled. Although the movement of mRNP complexes occurs without the expenditure of metabolic energy, ATP is required for the complexes to resume their motion after they become stalled. This finding provides an explanation for a number of observations in which mRNA transport appeared to be an enzymatically facilitated process.

The rules and roles of nucleocytoplasmic shuttling proteins

Febs Letters, 2001

The spatial separation of mRNA synthesis from translation, while providing eukaryotes with the possibility to achieve higher complexity through a more elaborate regulation of gene expression, has set the need for transport mechanisms through the nuclear envelope. In a simplistic view of nucleocytoplasmic transport, nuclear proteins are imported into the nucleus while RNAs are exported to the cytoplasm. The reality is, however, that transport of either proteins or RNAs across the nuclear envelope can be bi-directional. During the past years, an increasing number of proteins have been identified that shuttle continuously back and forth between the nucleus and the cytoplasm. The emerging picture is that shuttling proteins are key factors in conveying information on nuclear and cytoplasmic activities within the cell. ß

The Mechanism of Nucleocytoplasmic Transport through the Nuclear Pore Complex

Cold Spring Harbor Symposia on Quantitative Biology, 2010

Unlike their prokaryotic ancestors, eukaryotic cells contain numerous membrane-bound organelles that compartmentalize various specialized processes. This evolutionary advancement enabled tighter regulation of cellular functions but meant that cells needed to develop channels to transport proteins, ions, and other substances specifically across their internal and external membranes. Of all of the transport channels in a cell, one stands out from all of the others in terms of the range and size of cargoes that pass through it. This is the NPC, which mediates all transport across the nuclear envelope (NE) (the double-membraned layer that separates the nuclear genetic material from the cytoplasm). Transport through the NPC is rapid and bidirectional, with a large set of diverse cargoes crossing between the nucleus and cytoplasm. Cargoes such as transcription factors, ribosomal proteins, and viral nucleic acids enter the nucleus, whereas, messenger ribonucleoproteins (mRNPs), transfer RNAs (tRNAs), and ribosomal subunits exit. Despite the wide range of molecules that must pass through the NPC, nucleocytoplasmic transport is incredibly selective. Transport can also occur very quickly, up to the order of thousands of events per NPC per second (Ribbeck and Gorlich 2001). Yet the structure of the NPC, discussed below, has been found to be surprisingly simple. How this simple structure might mediate this rapid yet selective transport of such a variety of cargoes remains the main question in the field and is the major topic of this chapter. SOLUBLE PHASE OF TRANSPORT Karyopherin-Mediated Transport Numerous lines of evidence have shown that only proteins that can specifically bind to the family of nuclear pore proteins called FG nups are able to efficiently and rapidly cross the NPC. Many such FG-binding proteins act as transport factors, carrying non-FG-binding cargoes across the NPC. Karyopherins (Kaps), also known as importins and exportins, are a family of transport factors that carry proteins and protein/RNA complexes as large as 2 MDa across the NPC (Dworetzky and Feldherr 1988;

Nuclear transport and transcriptional regulation

FEBS Letters, 1999

Studies over the past 10 years have provided major insights into the molecular mechanisms responsible for active transport of macromolecules in and out of the nucleus. Nucleocytoplasmic transport pathways correspond to active and signal-mediated processes that involve substrates, adaptors and receptors. Regulation of both nuclear import and nuclear export is mainly exerted at the level of transport complex formation and has emerged as one of the most efficient mechanisms to adapt gene expression to the cell environment by restricting the access of transcriptional regulators to their target genes.