M04.01.006 The nucleus

The nucleus is a vital organelle in eukaryotic cells that houses the cell’s genetic material and controls various cellular functions. Here is a detailed overview of the physiology of the nucleus:

1. Structure and Composition:
   • The nucleus is a double-membrane organelle surrounded by the nuclear envelope, which consists of an outer nuclear membrane and an inner nuclear membrane with a narrow space between them called the perinuclear space.
   • Nuclear pores are embedded in the nuclear envelope, allowing the exchange of molecules between the nucleus and the cytoplasm.
   • The interior of the nucleus is filled with nucleoplasm, a gel-like substance containing chromatin, nucleoli, and various nuclear proteins.
2. Chromatin Structure and DNA Packaging:
   • Chromatin is the complex of DNA, histone proteins, and other associated proteins that make up the genetic material within the nucleus.
   • The DNA is organized into chromosomes during cell division, but during interphase, it exists as loosely packed chromatin, allowing access to genes for transcription and other nuclear processes.
   • Chromatin can undergo structural changes, such as condensation into more compact forms (heterochromatin) or relaxation into less condensed forms (euchromatin), depending on gene activity and cellular needs.
3. DNA Replication and Gene Expression:
   • The nucleus plays a crucial role in DNA replication and gene expression.
   • DNA replication occurs in the nucleus during the S phase of the cell cycle, where DNA polymerases and other enzymes synthesize a new complementary DNA strand.
   • Gene expression, including transcription and RNA processing, takes place within the nucleus. Transcription factors and RNA polymerases bind to specific regions of DNA, initiating the synthesis of messenger RNA (mRNA) molecules.
4. RNA Processing and Nuclear Export:
   • Within the nucleus, pre-mRNA molecules undergo various processing steps, including capping, splicing, and polyadenylation, to generate mature mRNA.
   • These processing steps occur in specialized nuclear compartments called spliceosomes and involve the removal of introns and the joining of exons.
   • After processing, mature mRNA molecules are transported out of the nucleus through nuclear pores for translation in the cytoplasm.
5. Nucleoli and Ribosome Biogenesis:
   • Nucleoli are distinct structures within the nucleus involved in the synthesis and assembly of ribosomes, the cellular machinery responsible for protein synthesis.
   • Nucleoli contain regions called nucleolar organizer regions (NORs), which consist of repeated DNA sequences that encode ribosomal RNA (rRNA).
   • Within the nucleoli, rRNA genes are transcribed and processed to generate mature rRNA, which combines with ribosomal proteins to form ribosomal subunits.
6. Nuclear Organization and Gene Regulation:
   • The nucleus exhibits a level of spatial organization that plays a role in gene regulation.
   • Chromosomes occupy specific territories within the nucleus, and interactions between different chromatin regions and nuclear proteins contribute to gene expression control.
   • The nuclear organization is dynamic, with chromosomes undergoing movement and repositioning in response to various stimuli and during cell division.

Understanding the detailed physiology of the nucleus is crucial for comprehending cellular processes such as DNA replication, gene expression, RNA processing, and nuclear organization. Dysfunctions in nuclear physiology can lead to various genetic disorders, developmental abnormalities, and diseases such as cancer. Further research into nuclear processes and their regulation is essential for advancing our understanding of cellular physiology and developing targeted therapies.