Nucleus

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Nucleus
Structure: The nucleus, the largest organelle of the cell, includes the nuclear envelope,
nucleolus, nucleoplasm, and chromatin and contains the genetic material encoded in the
deoxyribonucleic acid (DNA) of chromosomes.
Function: The nucleus directs protein synthesis in the cytoplasm via ribosomal ribonucleic
acid (rRNA), messenger RNA (mRNA), and transfer RNA (tRNA). All forms of RNA are
synthesized in the nucleus.
 Nuclear Envelope.
The nuclear envelope surrounds the nuclear material and consists of two parallel
membranes separated from each other by a narrow perinuclear cisterna. These
membranes fuse at intervals, forming openings in the nuclear envelope called nuclear
pores.
o Outer nuclear membrane
 This membrane is about 6 nanometers (nm) thick.
 It faces the cytoplasm and is continuous at certain sites with the rough
endoplasmic reticulum (RER).
 A loosely arranged mesh of intermediate filaments (vimentin) surrounds the outer
nuclear membrane on its cytoplasmic aspect.
 Ribosomes stud the cytoplasmic surface of the outer nuclear membrane .These
ribosomes synthesizes proteins that enter the perinuclear cisterna.
o Inner nuclear membrane
 The inner nuclear membrane is about 6 nm thick.
 It faces the nuclear material but is separated from it and supported on its inner
surface by the nuclear lamina, a fibrous lamina that is 80-300 nm thick and
composed primarily of lamins A, B, and C. These intermediate filament proteins help
organize the nuclear envelope and perinuclear chromatin. Additionally, they are
essential during the mitotic events, when they are responsible for the disassembly
and reassembly of the nuclear envelope. Phosphorylation of lamins leads to
disassembly,and dephosphorylation results in reassembly of the nuclear envelope.
o Perinuclear cisterna
 The perinuclear cisterna is located between the inner and outer nuclear membranes
and is 20-40 nm wide.
 It is continuous with the cisterna of the RER.
 It is perforated by nuclear pores at various locations.
o Nuclear pores
 Nuclear pores average 80 nm in diameter and number from dozens to thousands
depending upon metabolic activity; they are associated with the nuclear pore complex
(NPC).
 They are formed by fusion of the inner and outer nuclear membranes.
 They permit passage of certain molecules in either direction between the nucleus and
cytoplasm via a 9-nm channel opening.

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o The nuclear pore complex (NPC) represents protein subunits surrounding the nuclear
pore.
Function. The NPC permits passive movement across the nuclear envelope via a 9- to 11-nm
open channel for simple diffusion. Most proteins, regardless of size, pass in either direction
only by receptor-mediated transport. These proteins have clusters of certain amino acids
known as nuclear localization segments (NLS) that act as signals for transport.
Transport mechanisms involve a group of proteins, exportins and importins. These are
regulated by Ran, a group of guanosine triphosphatebinding proteins.
Nucleolus
Structure. The nucleolus is a nuclear inclusion that is not surrounded by a membrane. It is
present in cells that are actively synthesizing proteins; more than one nucleolus can be
present in the nucleus. It is generally detectable only when the cell is in interphase. It contains
mostly rRNA and protein as well as a modest amount of DNA. The nucleolus contains four
distinct regions.
o Fibrillar centers are composed of inactive DNA where DNA is not being transcribed.
o Pars fibrosa are composed of 5-nm fibrils surrounding the fibrillar centers and contain
transcriptionally active DNA and the rRNA precursors that are being transcribed.
o Pars granulosa are composed of 15-nm maturing ribosomal precursor particles.
o Nucleolar matrix is a fiber network participating in the organization of the nucleolus.
Function. The nucleolus is involved in the synthesis of rRNA and its assembly into ribosome
precursors. It has been determined that the nucleolus also sequesters certain nucleolar
proteins that function as cell-cycle checkpoint signaling proteins. Three such cell-cycle
regulator proteins have been identified within the nucleolus, where they remain sequestered
until their release is required for targets in the nucleus and/or cytoplasm.
Nucleoplasm
Nucleoplasm is the protoplasm within the nuclear envelope. It consists of a matrix and various
types of particles.
1) Nuclear matrix acts as a scaffold that aids in organizing the nucleoplasm.
 Structural components include fibrillar elements, nuclear porenuclear lamina
complex, residual nucleoli, and a residual ribonucleoprotein (RNP) network.
 Functional components are involved in the transcription and processing of mRNA
and rRNA, steroid receptor-binding sites, carcinogenbinding sites, heat-shock
proteins, DNA viruses, and viral proteins (T antigen) and perhaps many other
functions that are as yet not known.
2) Nuclear particles
 Interchromatin granules are clusters of irregularly distributed particles (20-25 nm in
diameter) that contain RNP and various enzymes.
 Perichromatin granules are single dense granules (30-50 nm in diameter) surrounded
by a less dense halo. They are located at the periphery of heterochromatin and exhibit
a substructure of 3-nm packed fibrils.
 Perichromatin granules contain 4.7S RNA and two peptides similar to those found
in heterogeneous nuclear RNPs (hnRNPs).

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 They may represent messenger RNPs (mRNPs).
 The number of granules increases in liver cells exposed to carcinogens or
temperatures above 37°C.
 The hnRNP particles are complexes of precursor mRNA (premRNA) and proteins and
are involved in processing of pre-mRNA.
 Small nuclear RNPs (snRNPs) are complexes of proteins and small RNAs and are
involved in hnRNP splicing or in cleavage reactions.
Chromatin
Structure. Chromatin consists of double-stranded DNA complexed with histones and acidic
proteins. It resides within the nucleus as heterochromatin and euchromatin. The euchromatin-
heterochromatin ratio is higher in malignant cells than in normal cells.
 Heterochromatin, condensed inactive chromatin, is concentrated at the periphery of the
nucleus and around the nucleolus, as well as scattered throughout the nucleoplasm.
 When examined under the light microscope (LM), it appears as basophilic clumps of
nucleoprotein.
 Although it is transcriptionally inactive, recent evidence indicates that heterochromatin
plays a role in interchromosomal interactions and chromosomal segregation during
meiosis.
 Heterochromatin corresponds to one of two X chromosomes and is therefore present in
nearly all somatic cells of female mammals. During interphase, the inactive X
chromosome is visible as a dark-staining body within the nucleus. This structure is
called the Barr body, or sex chromatin.
 Euchromatin is the transcriptionally active form of chromatin that appears in the LM as a
lightly stained region of the nucleus. It appears in transmission electron microscope (TEM)
as electron-lucent regions among heterochromatin, and is composed of 30-nm strings of
nucleosomes and the DNA double helix.
Function. Chromatin is responsible for RNA synthesis.
Chromosomes
Structure. Chromosomes consist of chromatin extensively folded into loops; this conformation
is maintained by DNA-binding proteins. Each chromosome contains a single DNA molecule
and associated proteins, assembled into nucleosomes, the structural unit of chromatin pack
aging. Chromosomes are visible with the LM only during mitosis and meiosis when their
chromatin condenses.
Extended chromatin forms the nucleosome core, around which the DNA double helix is
wrapped two full turns.
 The nucleosome core consists of two copies each of histones H2A, H2B, H3, and H4.
Nucleosomes are spaced at intervals of 200 base pairs.
 When viewed with TEM, extended chromatin resembles "beads on a string;" the beads
represent nucleosomes and the string represents linker DNA.
Condensed chromatin contains an additional histone, H1, which wraps around groups
of nucleosomes forming 30-nm-diameter fibers, the structural unit of the chromosome.
 Haploid number (n) is the number of chromosomes in germ cells (23 in humans).
 Diploid number (2n) is the number of chromosomes in somatic cells (46 in humans).

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Genome is the total genetic complement of an individual, and is stored in its chromosomes. In
humans, the genome consists of 22 pairs of autosomes and 1 pair of sex chromosomes (either
XX or XY), totaling 46 chromosomes.
DNA. DNA is a long, double-stranded, linear molecule composed of multiple nucleotide
sequences. It acts as a template for the synthesis of RNA.
Nucleotides are composed of a base (purine or pyrimidine), a deoxyribose sugar, and a
phosphate group.
The purines are adenine (A) and guanine (G).Pyrimidines are cytosine (C) and thymine (T).
The DNA double helix consists of two complementary DNA strands held together by
hydrogen bonds between the base pairs A-T and G-C.
A codon is a sequence of three bases in the DNA molecule that codes for a single amino acid.
A gene is a segment of the DNA molecule that is responsible for the formation of a single RNA
molecule.
RNA. RNA is a linear molecule similar to DNA, however, it is single stranded and contains
ribose instead of deoxyribose sugar and uracil (U) instead of thymine (T). RNA is synthesized
by transcription of DNA. Transcription is catalyzed by three RNA polymerases: I for rRNA, II for
mRNA, and III for tRNA. mRNA carries the genetic code to the cytoplasm to direct protein
synthesis .
tRNA is folded into a cloverleaf shape and contains about 80 nucleotides, terminating in
adenylic acid (where amino acids attach).
Each tRNA combines with a specific amino acid that has been activated by an enzyme.
One end of the tRNA molecule possesses an anticodon, a triplet of nucleotides that recognizes
the complementary codon in mRNA. If recognition occurs, the anticodon ensures that the
tRNA transfers its activate9 amino acid molecule in the proper sequence to the growing
polypeptide chain.
Ribosomal RNA associates with many different proteins (including enzymes) to form
ribosomes. rRNA associates with mRNA and tRNA during protein synthesis.