The Nucleus: Structure, Function, and Transport Mechanisms

The Nucleus

Overview and Functions

The nucleus is a membrane-bound organelle found in eukaryotic cells, serving as the repository for genetic material and the site of key cellular processes. It is essential for the regulation of gene expression and the maintenance of genome integrity.

• Chromosomes are localized within the nucleus, ensuring organized storage and access to DNA.

• DNA replication occurs in the nucleus, allowing genetic information to be faithfully copied during cell division.

• DNA transcription takes place in the nucleus, producing RNA molecules from DNA templates.

• Post-transcriptional modification of RNA, such as splicing and capping, is also performed within the nucleus.

• Example: In human cells, the nucleus contains 46 chromosomes, each composed of DNA and associated proteins.

Nucleus: Structure

Major Components

The nucleus is composed of several distinct structural elements that contribute to its function and organization.

• Nuclear envelope: A double-membrane structure that separates the nucleus from the cytoplasm.

  • Outer membrane: Continuous with the endoplasmic reticulum and studded with ribosomes.

  • Inner membrane: Lined by the nuclear lamina, providing structural support.

  • Perinuclear space: The gap between the inner and outer membranes, typically 20–40 nm wide.

• Nucleoplasm: The semi-fluid matrix within the nucleus, containing chromatin and nuclear bodies.

• Nucleolus: A dense region within the nucleus responsible for ribosome biogenesis.

Nucleolus

Structure and Function

The nucleolus is a prominent sub-nuclear structure involved in the synthesis and assembly of ribosomal subunits.

• Assembly of ribosomal subunits: Ribosomal RNA (rRNA) is transcribed and combined with proteins to form ribosome precursors.

• Fibrils: Regions containing newly transcribed rRNA.

• Granules: Areas where ribosomal subunits are assembled and stored.

• Example: The nucleolus disappears during mitosis and reappears in daughter nuclei.

Nuclear Lamina

Structure and Role

The nuclear lamina is a dense network of intermediate filaments that provides mechanical support to the nucleus.

• Dense meshwork of fibers: Composed primarily of lamins, a type of intermediate filament protein.

• Lines the inner surface of the nuclear membrane: Anchors chromatin and nuclear pores, maintaining nuclear shape.

• Made of lamins: Mutations in lamin genes can lead to diseases such as progeria.

• Example: The nuclear lamina disassembles during cell division and reassembles in daughter nuclei.

Nuclear Pores and Transport

Nuclear Pore Complex (NPC)

The nuclear pore complex (NPC) is a large protein assembly embedded in the nuclear envelope, facilitating selective transport between the nucleus and cytoplasm.

• Specialized channels: NPCs allow passive diffusion of small molecules and ions, and active transport of macromolecules.

• Octagonal symmetry: NPCs are built from multiple nucleoporins arranged in an octagonal pattern.

• Aqueous diffusion channel: Permits free movement of molecules up to ~40 kDa.

• Active transport: Larger molecules (e.g., proteins, RNAs) require specific transport signals.

Export Through NPC

• Mature tRNA, mRNA, and ribosomal subunits are exported from the nucleus to the cytoplasm via NPCs.

Import Through NPC

• Histones, nucleic acid polymerases, gene regulatory proteins, and RNA processing proteins are imported into the nucleus.

Nuclear Transport Mechanisms

Import Process

Proteins destined for the nucleus contain a nuclear localization signal (NLS) that is recognized by importin proteins.

1. Cargo binds importin: The NLS on the cargo protein is recognized by importin (composed of alpha and beta subunits).

2. Cargo-importin complex translocates into the nucleus through the NPC.

3. Importin binds Ran-GTP: In the nucleus, Ran-GTP binds importin, causing cargo release.

4. Ran-importin complex returns to cytosol: Importin is released from Ran-GTP by GTP hydrolysis, mediated by GTPase-activating proteins.

Export Process

RNA and proteins exported from the nucleus contain a nuclear export signal (NES) recognized by exportin proteins.

1. RNA cargo binds exportin: NES is recognized by exportin, which also binds Ran-GTP.

2. Export through NPC: The complex translocates through the NPC to the cytoplasm.

3. Ran-GTP hydrolyzed: Hydrolysis of GTP releases the cargo in the cytoplasm.

Key Equations and Concepts

• Passive diffusion limit: Molecules < 40 kDa can diffuse freely through NPCs.

• Active transport: Requires energy and specific signals (NLS or NES).

Summary Table: Nuclear Structures and Functions

Structure	Main Components	Function
Nuclear Envelope	Outer & Inner Membranes, Perinuclear Space	Separates nucleus from cytoplasm
Nucleolus	Fibrils, Granules	Ribosome subunit assembly
Nuclear Lamina	Lamins	Structural support, chromatin organization
Nuclear Pore Complex	Nucleoporins	Transport of molecules

Additional info: The notes have been expanded to include definitions, examples, and a summary table for clarity and completeness.