The Eukaryote Nucleus
BIO 224
Intro to Cell and Molecular Biology
Nucleus
• The control center of the cell• Holds the cell’s genetic information• Site of DNA replication, transcription, and
RNA processing• Defining feature of eukaryotic cells• Separates the genome translation
process, plays a major role in eukaryote gene expression
The Nuclear Envelope
• Separates the nuclear contents from the cytoplasm and provides structural support for the nucleus
• Maintains the nucleus as a distinct biochemical compartment
• Has two membranes, nuclear pore complexes, and an underlying lamina
Nuclear Envelope Membranes
• Each membrane is a phospholipid bilayer• Outer membrane is continuous with ER
– Has a similar function to the membrane of the ER – Has ribosomes on the cytoplasmic surface
• Inner membrane has nucleus specific proteins– The proteins bind it to the nuclear lamina
• Membranes are joined at pore complexes– The only place macromolecules and small polar
molecules may pass– Convey RNAs between the nucleus and cytoplasm
Nuclear Pore Complex
• The only channels for small polar molecules, ions, macromolecules (proteins and RNA) to travel between the nucleus and cytoplasm
• 120nm in diameter, 125 MD mass• The nuclear pore of vertebrates is a complex
of 30-50 nucleoporins• Control traffic between the nucleus and
cytoplasm, play a role in eukaryote cell physiology
Nuclear Lamina
• A fibrous meshwork that provides structural support to the nucleus
• Made of 60-80 kD intermediate protein filaments called lamins
• Filaments associate with one another to form complex higher order structures
• Associate with the internal face of the inner nuclear membrane via lipid and protein interactions
Model of lamin assembly
The nuclear lamina
Nuclear Protein Transport• Proteins imported from the cytoplasm to the nucleus are responsible for
genome structure and function– Histones, DNA and RNA polymerases, Transcription factors
• Proteins targeted to the nucleus by nuclear localization signals– Recognized by transport receptors and direct the transport of proteins
through the pore complex• Karyopherin family nuclear of transport receptors function as importins or exprotins
in response to recognition of the nuclear localization signals• Nuclear export signals target proteins for export from the nucleus
– Specific AA signals that are recognized by exportins• Ran is a protein that (in association with GTP) regulates passage of
macromolecules through the nuclear pore– Regulation of protein transport allows for control of nuclear proteins and gene
expression• Plays a role in cellular response to environmental change
– Allows cell surface signals to be transmitted to the nucleus– Regulates import of transcription factors and protein kinases
Nuclear Transport of RNA
• Most RNAs exported from nucleus to cytoplasm– mRNAs, rRNAs, tRNAs
• Transport receptors interact with the nuclear pore complex and use energy
• Importins and exportins transport most tRNAs, rRNAs and snRNAs using Ran/GTP pathway
• mRNAs exported by a 2 protein “mRNA exporter” complex independently of Ran
Nuclear Transport of RNA
• RNAs are transported as RNPs (ribonucleoprotein complexes)
• rRNAs are associated with ribosomal proteins and specific RNA processing proteins – Subunits exported to the cytoplasm
• Pre-mRNAs and mRNAs associate with a set of 20 proteins during processing and transport
• tRNAs are exported by exportin-t• Small RNAs (snRNAs & snoRNAs) function in the
nucleus to help with RNA processing– snRNAs exported to cytoplasm to associate with proteins to
becom snRNPs and reenter nucleus to function
Internal Nuclear Organization
• The nucleus’ internal structure organizes genetic material and localizes nuclear functions
• Nuclear lamins act as chromatin attachment sites and to organize proteins
• Lamin dependent complexes involved in DNA repair, chromatin organization, gene regulation, and signal transduction
• Chromatin organized into large loops of DNA
Chromosomes and Chromatin Structure
• Chromatin condenses during mitosis to form compact chromosomes of metaphase
• Heterochromatin remains highly condensed and transcriptionally inactive during interphase
• 2 types of heterochromatin• Constitutive: DNA sequences aren’t transcribed• Facultative: DNA sequences transcribed in some cell
types• Euchromatin decondenses and is distributed through
nucleus during interphase• Chromosomes in interphase chromatin arranged in
organized fashion and divided into functional domains with roles in regulating gene expression
Nuclear Sub-compartments• Most nuclear processes localized to distinct regions:
subnuclear bodies• It is not fully understood how or why• Mammal nuclei have clustered sites of DNA replication
where multiple molecules are replicated• mRNA processing machinery concentrated in discrete
bodies called nuclear speckles• PML bodies are sites of localization of transcriptional
regulatory proteins involved in acute promyelocytic leukemia– Interact with chromatin and are sites of accumulation of
transcription factors and chromatin modifying proteins• Cajal bodies have coilin protein and small RNPs
– Thought to be site of RNP assembly and snRNP processing
The Nucleolus• Site of rRNA transcription and processing and ribosome
assembly• General role in modification of RNA• Site of transcription of ribosomal subunit genes • Important in oocytes where genes need to be amplified
to support increased numbers of ribosomes needed in early embryonic development
• Divided into three regions: fibrillar center, dense fibrillar component, granular component– Sites of progressive stages of rRNA transcription, processing,
and ribosome assembly• Ribosomes assembled from ribosomal precursor RNA,
ribosomal proteins, and 5S rRNA
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