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Nuclear Structure and Function
Research Guide
What is Nuclear Structure and Function?
Nuclear Structure and Function is the study of how the cell nucleus is organized—across the nuclear envelope, nuclear pores, lamina, chromatin, and nuclear bodies—and how that organization controls genome stability, gene expression, and nucleo‑cytoplasmic exchange in health and disease.
Nuclear Structure and Function spans mechanistic work on nuclear transport, nuclear envelope/lamina integrity, chromatin-end protection, and mesoscale nuclear organization such as biomolecular condensates.
Topic Hierarchy
Research Sub-Topics
Nuclear Pore Complex Structure
Nuclear pore complex (NPC) structure research employs cryo-EM and super-resolution microscopy to resolve scaffold and FG-nucleoporin organization. Researchers model 8-fold symmetric architecture and gating mechanisms at Angstrom resolution.
Nucleocytoplasmic Transport Mechanisms
Nucleocytoplasmic transport studies nuclear import/export pathways mediated by karyopherins, Ran GTPase gradients, and FG-repeat barriers. Researchers dissect directionality, cargo specificity, and regulation by post-translational modifications.
Nuclear Lamins Function
Nuclear lamins research explores A/C and B-type lamins in nuclear envelope mechanics, chromatin tethering, and gene regulation. Researchers investigate lamin polymer dynamics, interactions, and mutations in laminopathies.
Nuclear Envelope Dynamics
Nuclear envelope dynamics examines assembly/disassembly during cell division, rupture/repair events, and lipid composition regulation. Researchers use live-cell imaging to study NE reformation and intranuclear envelope tubules.
Nuclear Mechanics
Nuclear mechanics investigates nuclear deformability, mechanotransduction, and force transmission via LINC complex and lamina. Researchers quantify viscoelastic properties and responses to cytoskeletal forces in confined migration.
Why It Matters
Defects in nuclear structure and transport have direct, clinically relevant consequences because they alter genome maintenance and gene-regulatory programs that cells rely on to remain viable and differentiated. A concrete example is Hutchinson–Gilford progeria syndrome: "Recurrent de novo point mutations in lamin A cause Hutchinson–Gilford progeria syndrome" (2003) identified recurrent de novo point mutations in lamin A that link nuclear-lamina disruption to a severe human premature-aging disease. Nuclear transport is also central to gene regulation by small RNAs: Yi et al. (2003) showed in "Exportin-5 mediates the nuclear export of pre-microRNAs and short hairpin RNAs" that Exportin-5 mediates nuclear export of pre‑microRNAs and short hairpin RNAs, and Lund et al. (2003) showed in "Nuclear Export of MicroRNA Precursors" that Exportin‑5 mediates efficient export of short miRNA precursors; together these results connect nuclear pore–dependent trafficking to the production of mature microRNAs that regulate mRNA expression programs. At the level of nuclear organization, Shin and Brangwynne (2017) argued in "Liquid phase condensation in cell physiology and disease" that phase separation helps organize intracellular biochemistry, and Hyman et al. (2014) explained in "Liquid-Liquid Phase Separation in Biology" how liquid-like compartments can form without membranes; these concepts are widely used to interpret how nuclear bodies and chromatin-associated assemblies can concentrate factors to control transcription, RNA processing, and stress responses. Methodologically, Roux et al. (2012) introduced proximity-dependent labeling in "A promiscuous biotin ligase fusion protein identifies proximal and interacting proteins in mammalian cells," enabling mapping of local nuclear neighborhoods (for example, at the nuclear envelope or within nuclear bodies) that are difficult to capture by classic co-immunoprecipitation.
Reading Guide
Where to Start
Start with "Liquid-Liquid Phase Separation in Biology" (2014) because it lays out the core physical concepts and vocabulary needed to interpret many modern papers on nuclear bodies and nuclear organization.
Key Papers Explained
Hyman et al. (2014) in "Liquid-Liquid Phase Separation in Biology" provides the physical basis for liquid-like cellular compartments, and Shin and Brangwynne (2017) in "Liquid phase condensation in cell physiology and disease" connects those principles to physiological function and disease relevance. In parallel, Yi et al. (2003) in "Exportin-5 mediates the nuclear export of pre-microRNAs and short hairpin RNAs" and Lund et al. (2003) in "Nuclear Export of MicroRNA Precursors" establish a concrete, experimentally tractable nuclear-transport pathway (Exportin‑5) that links nuclear trafficking to gene regulation by miRNAs. de Lange (2005) in "Shelterin: the protein complex that shapes and safeguards human telomeres" anchors nuclear function in genome-end protection, while Eriksson et al. (2003) in "Recurrent de novo point mutations in lamin A cause Hutchinson–Gilford progeria syndrome" shows how perturbing a core architectural component (lamin A) produces a defined human disease, motivating mechanistic connections between structure, mechanics, and gene control.
Paper Timeline
Most-cited paper highlighted in red. Papers ordered chronologically.
Advanced Directions
A practical advanced direction is to combine proximity labeling and organization models: use the strategy from "A promiscuous biotin ligase fusion protein identifies proximal and interacting proteins in mammalian cells" (2012) to map local proteomes of nuclear assemblies whose formation is interpreted through "Liquid-Liquid Phase Separation in Biology" (2014) and "Liquid phase condensation in cell physiology and disease" (2017), while testing how disease-linked architectural changes such as those in "Recurrent de novo point mutations in lamin A cause Hutchinson–Gilford progeria syndrome" (2003) reshape those neighborhoods and alter RNA-export pathways described in the two Exportin‑5 papers (2003).
Papers at a Glance
| # | Paper | Year | Venue | Citations | Open Access |
|---|---|---|---|---|---|
| 1 | Liquid phase condensation in cell physiology and disease | 2017 | Science | 4.1K | ✕ |
| 2 | Association of missense and 5′-splice-site mutations in tau wi... | 1998 | Nature | 3.5K | ✕ |
| 3 | Liquid-Liquid Phase Separation in Biology | 2014 | Annual Review of Cell ... | 3.1K | ✕ |
| 4 | Shelterin: the protein complex that shapes and safeguards huma... | 2005 | Genes & Development | 3.0K | ✓ |
| 5 | Exportin-5 mediates the nuclear export of pre-microRNAs and sh... | 2003 | Genes & Development | 2.9K | ✓ |
| 6 | Nuclear Export of MicroRNA Precursors | 2003 | Science | 2.7K | ✕ |
| 7 | Phase transitions in the assembly of multivalent signalling pr... | 2012 | Nature | 2.6K | ✕ |
| 8 | A promiscuous biotin ligase fusion protein identifies proximal... | 2012 | The Journal of Cell Bi... | 2.5K | ✓ |
| 9 | Data on the distribution of fibre types in thirty-six human mu... | 1973 | Journal of the Neurolo... | 2.2K | ✕ |
| 10 | Recurrent de novo point mutations in lamin A cause Hutchinson–... | 2003 | Nature | 2.1K | ✓ |
In the News
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Code & Tools
## Repository files navigation # 🍝 nudel – Nuclear Data Extraction Library License Nudel is a parser for the Evaluated Nuclear Structure Data...
**GIDI+**is a collection of C++ libraries for accessing evaluated and processed nuclear data stored in the Generalized Nuclear Database Structure (...
A module to parse nuclear data from the ENSDF and aimed at facilitating the use of the decay data flexibly for other purposes like representation a...
## Repository files navigation # NPAT NPAT (nuclear physics analysis tools) is a python toolkit developed to aid in the analysis of experimental ...
(particle) transport applications built for parallel computing hardware. It consists of semi-independent packages and a robust build system. The pa...
Recent Preprints
(PDF) Structure and Function in the Nucleus
StructureandFunctionintheNucleus AngusI.Lamond\*andWilliamC.Earnshaw Currentevidencesuggeststhatthenucleushasadistinctsubstructure,albeitonethat isdynamicratherthanarigidframework.Viralinfection...
Nucleus | Journal
Chromatin organization Nuclear transport DNA replication and DNA damage repair Gene expression and RNA processing Nucleus in signaling and development Nuclear proteomics, lipidomics and metabolomic...
An integrated view of the structure and function of the human 4D nucleome
The dynamic three-dimensional (3D) organization of the human genome (the 4D nucleome) is linked to genome function. Here we describe efforts by the 4D Nucleome Project 1 to map and analyse the 4D n...
Nuclear Structure
The low-energy nuclear structure group leads a scientific program focused on studying and understanding the structure of nuclei at the limits -- of existence, of spin, etc. Our research is primari...
Nuclear chemistry - Latest research and news
Nuclear chemistry is concerned with the properties of and changes to atomic nuclei, as opposed to traditional chemistry, which involves properties and changes related to the electronic structure of...
Latest Developments
Recent developments in Nuclear Structure and Function research include advanced nuclear property predictions using the Frontier supercomputer at Oak Ridge National Laboratory, revealing detailed insights into nuclear shapes and rotations (RD World, Physical Review X), progress in designing safer, more cost-effective next-generation nuclear reactors (ORNL), and studies on nuclear reactions and shell evolution, such as abrupt structural transitions in exotic molybdenum isotopes and new findings on lanthanum isotopes' mass and shell structure (Nature Communications, arXiv).
Sources
Frequently Asked Questions
What does “Nuclear Structure and Function” mean in molecular biology research?
Nuclear Structure and Function refers to how the nucleus is physically organized (nuclear envelope, nuclear pores, lamina, chromatin, and nuclear bodies) and how that organization determines processes such as nucleocytoplasmic transport, genome stability, and gene regulation. "Liquid phase condensation in cell physiology and disease" (2017) and "Liquid-Liquid Phase Separation in Biology" (2014) are frequently cited frameworks for understanding non-membrane nuclear organization.
How are microRNA precursors transported from the nucleus to the cytoplasm?
Yi et al. (2003) showed in "Exportin-5 mediates the nuclear export of pre-microRNAs and short hairpin RNAs" that Exportin-5 mediates nuclear export of pre‑microRNAs and short hairpin RNAs. Lund et al. (2003) showed in "Nuclear Export of MicroRNA Precursors" that Exportin‑5 mediates efficient nuclear export of short miRNA precursors, linking nuclear export to miRNA maturation.
Why is lamin A central to nuclear mechanics and disease?
"Recurrent de novo point mutations in lamin A cause Hutchinson–Gilford progeria syndrome" (2003) connected recurrent de novo point mutations in lamin A to Hutchinson–Gilford progeria syndrome, directly implicating the nuclear lamina in a human disease phenotype. This anchors lamin A/C research as a mechanistic bridge between nuclear architecture and organismal pathology.
How do researchers explain membrane-less nuclear compartments and nuclear bodies?
Hyman et al. (2014) described in "Liquid-Liquid Phase Separation in Biology" how liquid-like compartments can form by phase separation, providing a physical basis for membrane-less organization. Shin and Brangwynne (2017) extended this in "Liquid phase condensation in cell physiology and disease" by discussing how condensation can organize physiology and contribute to disease.
Which methods help map protein neighborhoods inside the nucleus when interactions are transient or hard to solubilize?
Roux et al. (2012) presented in "A promiscuous biotin ligase fusion protein identifies proximal and interacting proteins in mammalian cells" a proximity-dependent labeling strategy (BioID) that identifies proteins near a bait in living cells. This approach is widely used to infer local nuclear environments where classical pull-downs can miss weak or spatially constrained associations.
Which classic nuclear structure problem connects chromosome ends to nuclear function?
de Lange (2005) synthesized how telomere ends are protected by a six-protein complex in "Shelterin: the protein complex that shapes and safeguards human telomeres." Telomere protection is a nuclear function tightly linked to genome stability, DNA damage signaling, and long-term cell viability.
Open Research Questions
- ? Which molecular features determine whether a given nuclear assembly behaves as a liquid-like condensate versus a more solid or gel-like state in vivo, as framed by "Liquid-Liquid Phase Separation in Biology" (2014) and "Liquid phase condensation in cell physiology and disease" (2017)?
- ? How do lamin A–linked structural perturbations propagate from the nuclear lamina to downstream genome regulation and cellular phenotypes in Hutchinson–Gilford progeria syndrome beyond the causal mutations described in "Recurrent de novo point mutations in lamin A cause Hutchinson–Gilford progeria syndrome" (2003)?
- ? What are the complete, context-dependent proximal protein environments of key nuclear structures (for example, nuclear envelope subdomains or nuclear bodies) that can be systematically captured using the strategy in "A promiscuous biotin ligase fusion protein identifies proximal and interacting proteins in mammalian cells" (2012)?
- ? Which regulatory checkpoints modulate Exportin‑5–dependent export flux for different RNA hairpins across conditions, building on the mechanism established in "Exportin-5 mediates the nuclear export of pre-microRNAs and short hairpin RNAs" (2003) and "Nuclear Export of MicroRNA Precursors" (2003)?
- ? How do telomere-protective mechanisms summarized in "Shelterin: the protein complex that shapes and safeguards human telomeres" (2005) interface with nuclear organization principles such as condensation and compartmentalization to tune DNA damage responses at chromosome ends?
Recent Trends
Across the provided core papers, a prominent trend is the use of phase-separation language to interpret nuclear organization: "Liquid-Liquid Phase Separation in Biology" and "Liquid phase condensation in cell physiology and disease" (2017) are among the most-cited works in the list (3136 and 4134 citations, respectively), reflecting broad uptake of condensate-based explanations for nuclear compartmentalization.
2014In parallel, nuclear transport remains a central mechanistic pillar for gene regulation, with the two Exportin‑5 studies—"Exportin-5 mediates the nuclear export of pre-microRNAs and short hairpin RNAs" (2003; 2945 citations) and "Nuclear Export of MicroRNA Precursors" (2003; 2669 citations)—serving as heavily cited references for how nuclear trafficking connects to miRNA biogenesis.
Disease-anchored nuclear architecture work is exemplified by "Recurrent de novo point mutations in lamin A cause Hutchinson–Gilford progeria syndrome" (2003; 2150 citations), which continues to motivate studies linking nuclear mechanics to pathology.
At the scale of the literature cluster, the provided dataset reports 279,124 works associated with Nuclear Structure and Function.
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