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What is the primary function of box C+D snoRNAs?
What is the primary function of box C+D snoRNAs?
Box H+ACA snoRNA is responsible for the methylation of riboses in rRNA.
Box H+ACA snoRNA is responsible for the methylation of riboses in rRNA.
False
What are the two major classes of snoRNAs?
What are the two major classes of snoRNAs?
box C+D snoRNAs and box H+ACA snoRNAs
The conversion of uridine to pseudouridine involves rotation of the __________ ring.
The conversion of uridine to pseudouridine involves rotation of the __________ ring.
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What is the approximate time it takes for the maturation and processing of the large ribosomal subunit?
What is the approximate time it takes for the maturation and processing of the large ribosomal subunit?
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Match the following components with their corresponding functions:
Match the following components with their corresponding functions:
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Nucleoli disassemble during mitosis when chromosomes condense.
Nucleoli disassemble during mitosis when chromosomes condense.
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What is one of the primary energy sources required for the formation of ribosomal subunits?
What is one of the primary energy sources required for the formation of ribosomal subunits?
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What is the primary function of nucleoli?
What is the primary function of nucleoli?
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Nucleoli are membrane-bound structures within the nucleus.
Nucleoli are membrane-bound structures within the nucleus.
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What are the three important steps involved in ribosome biogenesis?
What are the three important steps involved in ribosome biogenesis?
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Nuclear bodies represent multiple structures such as Cajal bodies, clastosomes, and _______.
Nuclear bodies represent multiple structures such as Cajal bodies, clastosomes, and _______.
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Which of the following statements about nucleolar stress is true?
Which of the following statements about nucleolar stress is true?
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What controls nucleocytoplasmic transport in the nucleus?
What controls nucleocytoplasmic transport in the nucleus?
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Match the following components with their respective descriptions:
Match the following components with their respective descriptions:
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In response to heat stress, ___________ bodies are formed in cells.
In response to heat stress, ___________ bodies are formed in cells.
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What is the main function of the fibrillar center (FC) in the nucleolus?
What is the main function of the fibrillar center (FC) in the nucleolus?
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The small ribosomal subunit contains three rRNA molecules.
The small ribosomal subunit contains three rRNA molecules.
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What is the role of nucleophosmin (NPM1) in the nucleolus?
What is the role of nucleophosmin (NPM1) in the nucleolus?
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The large ribosomal subunit (60S) contains rRNAs 28S, 5.8S, and ______.
The large ribosomal subunit (60S) contains rRNAs 28S, 5.8S, and ______.
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Match the nucleolar components with their functions:
Match the nucleolar components with their functions:
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What percentage of total RNA in cells is comprised of ribosomal RNA (rRNA)?
What percentage of total RNA in cells is comprised of ribosomal RNA (rRNA)?
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The ribosome is composed of rRNA and proteins only.
The ribosome is composed of rRNA and proteins only.
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What is the sedimentation rate of ribosomal subunits commonly designated in?
What is the sedimentation rate of ribosomal subunits commonly designated in?
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What is the primary role of the Detention Center within the nucleolus?
What is the primary role of the Detention Center within the nucleolus?
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70% of proteins found in nucleoli are involved in ribosome subunit biogenesis.
70% of proteins found in nucleoli are involved in ribosome subunit biogenesis.
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What is the role of the protein p53 in cellular processes?
What is the role of the protein p53 in cellular processes?
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The active form of p53 is a __________, which binds to responsive elements of relevant genes.
The active form of p53 is a __________, which binds to responsive elements of relevant genes.
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Match the following components to their functions:
Match the following components to their functions:
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What percentage of human cancers involve mutations in the TP53 gene?
What percentage of human cancers involve mutations in the TP53 gene?
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During which phase can RNA Polymerase I transiently leave active rRNA genes?
During which phase can RNA Polymerase I transiently leave active rRNA genes?
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Mutations in the TP53 gene can potentially give rise to proteins with oncogenic properties.
Mutations in the TP53 gene can potentially give rise to proteins with oncogenic properties.
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Alu RNA is not important for the formation of the nucleolus.
Alu RNA is not important for the formation of the nucleolus.
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What occurs in the G2-phase regarding nucleolar architecture?
What occurs in the G2-phase regarding nucleolar architecture?
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What is the main impact of nucleolar stress on ribosome formation?
What is the main impact of nucleolar stress on ribosome formation?
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Alu elements represent more than ____% of the human genome.
Alu elements represent more than ____% of the human genome.
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Match the following phases with their key nucleolar characteristics:
Match the following phases with their key nucleolar characteristics:
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What happens if cells are treated with amanitin?
What happens if cells are treated with amanitin?
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Under stress, nucleoli maintain their regular size and function.
Under stress, nucleoli maintain their regular size and function.
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What is the key function of aluRNA in the nucleolus?
What is the key function of aluRNA in the nucleolus?
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What is the primary function of the p53 protein when activated?
What is the primary function of the p53 protein when activated?
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The interaction of p53 with MDM2 leads to an increase in p53 levels within the cell.
The interaction of p53 with MDM2 leads to an increase in p53 levels within the cell.
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What role does ATM kinase play in the p53 signaling pathway?
What role does ATM kinase play in the p53 signaling pathway?
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Nucleolar stress allows ribosomal proteins to be released into the ______ and cytoplasm.
Nucleolar stress allows ribosomal proteins to be released into the ______ and cytoplasm.
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What happens to ribosomal proteins during nucleolar stress?
What happens to ribosomal proteins during nucleolar stress?
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The binding of MDM2 to nucleolar proteins decreases the availability of p53.
The binding of MDM2 to nucleolar proteins decreases the availability of p53.
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Name one nucleolar protein that can bind MDM2 and release p53.
Name one nucleolar protein that can bind MDM2 and release p53.
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Study Notes
Unit 13: Nucleolar Stress
- The nucleus is a large eukaryotic organelle containing DNA organized into different regions
- The nucleus has distinct nuclear bodies with high concentrations of specific proteins and RNAs
- Nuclear bodies have different names like Cajal bodies, clastosomes, histone locus bodies, nuclear speckles, nucleoli, paraspeckles, perinucleolar compartments, PML-nuclear bodies, and Polycomb bodies
- The nucleolus is the largest sub-compartment of the nucleus
- It is not bounded by a membrane and can occupy up to 25% of the nucleus
- Nucleoli are sites for rRNA (ribosomal RNA) synthesis
- Ribosomes are assembled in nucleoli
- rRNA genes are present in multiple copies in the cell
- rRNA genes consist of 18S, 5.8S, and 28S rRNA
- These genes are arranged in tandem arrays on specific chromosomes
- Pre-rRNA genes are transcribed by RNA polymerase I
- The exception is 5S rRNA, transcribed by RNA polymerase III
- Ribosomes are complex molecules composed of rRNA and proteins
- Ribosomal subunits are formed in the nucleolus and released into the cytoplasm
- Several chemical modifications and processing steps are needed for mature rRNA production
Functions and Internal Organization of Nucleoli
- Nucleoli are responsible for ribosome biogenesis, regulating cellular responses to stress
- Ribosome biogenesis involves transcription of pre-rRNA, processing of pre-rRNA, and assembly of ribosome subunits
- These events occur in different sub-compartments of the nucleolus (fibrillar center, dense fibrillar component, and granular component)
- Different subcomponents have distinctive densities and contain specific proteins
- Fibrillar center is the site of ribosomal RNA synthesis
- Dense fibrillar component processes pre-rRNA
- Granular component assembles ribosomal subunits
- rRNA incorporates with proteins to assemble into functional ribosomes
- Nucleophosmin (NPM1) is a critical protein in the granular component involved in nuclear export
Eukaryotic Pre-rRNA Transcript
- Cells contain multiple copies of rRNA genes
- rRNA genes encode 18S, 5.8S, and 28S rRNA
- Genes are arranged in a specific order (18S → 5.8S → 28S)
- Spacer regions between genes are different between species
- rRNA genes are arranged in tandem arrays in the nucleolus organizer regions (NORs) of multiple chromosomes
- Humans have ~200 copies of the rRNA gene per cell
Chemical Modification and Nucleolytic Processing of pre-rRNA in DFC
- rRNA fragments need to be separated for small and large ribosomal subunit formation
- Modifications (methylation and pseudouridylation) are critical for recruiting cleavage enzymes
- Small nucleolar RNAs (snoRNAs), associated with specific proteins, guide these modifications
- snoRNAs have specific structures (box C/D and box H/ACA) associated with different enzymes
- SnoRNAs help process pre-rRNA to yield mature rRNA
- Formation of pre-90S complex, precursor subunits (Pre-60S, Pre-40S formation) are critical steps
Cell Cycle-Dependent Nucleolar Dynamics
- Nucleolus forms around clusters of ribosomal genes called NORs on chromosomes, which contain genomic repeats for rRNA
- Nucleolus assembly and disassembly occur during the cell cycle
- M-phase: Nucleolus disassembles; UBF remains on active rRNA repeats
- G1-phase: Reassembly of nucleolus occurs around active NOR's
- S-phase: RNA polymerase I leaves the rRNA genes to prevent collisions with replication machinery
- G2-phase: large, fused nucleolus forms (possible inactive rDNA)
Stability and Stress-Induced Remodeling of Nucleolar Architecture
- Alu RNA, found in introns of many genes, acts as "glue" to form nucleoli
- Alu repeats are abundant in the human genome
- Alu RNA transcripts are synthesized by RNA polymerase II and III
- Alu RNA is crucial for nucleolus stability
- Stress stimuli lead to significant structural remodeling of nucleoli
The Multifunctional Role of Nucleolus
- Nucleoli contain many proteins (around 4500)
- Only 30% are involved in ribosome biogenesis
- The remaining 70% have other roles in stress responses
- Nucleolus acts as a hub for sensing and reacting to stimuli
- Nucleolar stress signal pathways rely on dynamic protein binding/release
Transcription Factor p53 Protein
- P53 is a transcription factor and tumor suppressor
- It has multiple domains (transactivation, DNA binding, oligomerization, etc.)
- P53 is regulated by MDM2, which promotes its degradation
- MDM2 is phosphorylated by ATM
- Active p53 is a tetramer that binds to specific DNA elements
- TP53 mutations frequently occur in cancers
p53 Signaling Pathway
- Stress stimuli activate ATM kinase, leading to p53 phosphorylation and stabilization
- Stabilized, phosphorylated p53 initiates apoptosis, cell cycle arrest, or DNA repair functions
- p53 levels are normally low due to binding and degradation by MDM2
- Stress induces p53 release from MDM2
- Nucleolus plays a role in p53 activation by releasing factors or changing p53 translation levels
Nucleolus at Normal Growth Conditions
- Nucleolus transcribes rRNAs using RNA polymerase I
- Simultaneously, ribosomal proteins (RPs) are produced
- RPs and rRNAs assemble into ribosomal subunits (40S and 60S) which are released into the cytoplasm
- p53 synthesis, ubiquitination, interaction with MDM2 and nuclear translocation are normal events
Nucleolus and Stress Response and p53 activation
- Stress induces nucleolar factor release into the nucleoplasm and cytoplasm
- Released factors can engage with MDM2, initiating the release of p53
- p53 levels increase, triggering downstream cellular responses
- RPL26 binds p53 mRNA to increase p53 levels
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Description
Explore the intricacies of the nucleus, focusing on nucleolar stress in this unit. Learn about various nuclear bodies, their functions, and the role of rRNA in ribosome assembly. Understand the transcription mechanisms involved and the genetic structure of rRNA genes.
