Unit 13: Nucleolar Stress
47 Questions
0 Views

Choose a study mode

Play Quiz
Study Flashcards
Spaced Repetition
Chat to Lesson

Podcast

Play an AI-generated podcast conversation about this lesson

Questions and Answers

What is the primary function of box C+D snoRNAs?

  • Conversion of uridine to pseudouridine
  • Modification of rRNA after transcription
  • Association with ribosomal proteins
  • Methylation of specific riboses (correct)

Box H+ACA snoRNA is responsible for the methylation of riboses in rRNA.

False (B)

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.

<p>pyrimidine</p> Signup and view all the answers

What is the approximate time it takes for the maturation and processing of the large ribosomal subunit?

<p>30 minutes (D)</p> Signup and view all the answers

Match the following components with their corresponding functions:

<p>Methyl transferase fibrillarin = Involved in pseudouridine conversion Pseudouridine synthase dyskerin = Methylation of riboses Pre-90S complex = Initial assembly of ribosomal subunits rDNA repeats = Forming nucleolar architecture</p> Signup and view all the answers

Nucleoli disassemble during mitosis when chromosomes condense.

<p>True (A)</p> Signup and view all the answers

What is one of the primary energy sources required for the formation of ribosomal subunits?

<p>GTPases and ATPases</p> Signup and view all the answers

What is the primary function of nucleoli?

<p>Ribosome biogenesis (C)</p> Signup and view all the answers

Nucleoli are membrane-bound structures within the nucleus.

<p>False (B)</p> Signup and view all the answers

What are the three important steps involved in ribosome biogenesis?

<p>Transcription of pre-rRNA, processing of pre-rRNA, assembly of ribosome subunits.</p> Signup and view all the answers

Nuclear bodies represent multiple structures such as Cajal bodies, clastosomes, and _______.

<p>nucleoli</p> Signup and view all the answers

Which of the following statements about nucleolar stress is true?

<p>p53 activation is involved in the response to nucleolar stress. (D)</p> Signup and view all the answers

What controls nucleocytoplasmic transport in the nucleus?

<p>Nuclear pore complexes.</p> Signup and view all the answers

Match the following components with their respective descriptions:

<p>Nuclear Envelope = Double-membrane structure enclosing the nucleus Heterochromatin = Condensed form of DNA Cajal Bodies = Nuclear body associated with RNA processing Nuclear Pore Complexes = Regulates transport in and out of the nucleus</p> Signup and view all the answers

In response to heat stress, ___________ bodies are formed in cells.

<p>nuclear stress</p> Signup and view all the answers

What is the main function of the fibrillar center (FC) in the nucleolus?

<p>Ribosomal RNA synthesis (C)</p> Signup and view all the answers

The small ribosomal subunit contains three rRNA molecules.

<p>False (B)</p> Signup and view all the answers

What is the role of nucleophosmin (NPM1) in the nucleolus?

<p>It serves as a nuclear export chaperone for ribosomal subunits.</p> Signup and view all the answers

The large ribosomal subunit (60S) contains rRNAs 28S, 5.8S, and ______.

<p>5S</p> Signup and view all the answers

Match the nucleolar components with their functions:

<p>Fibrillar Center = Ribosomal RNA synthesis Dense Fibrillar Component = Pre-rRNA processing Granular Component = Ribosomal subunit assembly Nucleophosmin = Nuclear export chaperone</p> Signup and view all the answers

What percentage of total RNA in cells is comprised of ribosomal RNA (rRNA)?

<p>80% (A)</p> Signup and view all the answers

The ribosome is composed of rRNA and proteins only.

<p>False (B)</p> Signup and view all the answers

What is the sedimentation rate of ribosomal subunits commonly designated in?

<p>Svedberg units (S)</p> Signup and view all the answers

What is the primary role of the Detention Center within the nucleolus?

<p>Structural remodeling of nucleoli (A)</p> Signup and view all the answers

70% of proteins found in nucleoli are involved in ribosome subunit biogenesis.

<p>False (B)</p> Signup and view all the answers

What is the role of the protein p53 in cellular processes?

<p>Regulates apoptosis, cell cycle, DNA replication and repair.</p> Signup and view all the answers

The active form of p53 is a __________, which binds to responsive elements of relevant genes.

<p>tetramer</p> Signup and view all the answers

Match the following components to their functions:

<p>p53 = Tumor suppressor and guardian of the genome MDM2 = Inhibitor of p53 Detention Center = Site of transcriptional inactivation Nucleolus = Hub for stress signaling</p> Signup and view all the answers

What percentage of human cancers involve mutations in the TP53 gene?

<blockquote> <p>50% (B)</p> </blockquote> Signup and view all the answers

During which phase can RNA Polymerase I transiently leave active rRNA genes?

<p>S-phase (A)</p> Signup and view all the answers

Mutations in the TP53 gene can potentially give rise to proteins with oncogenic properties.

<p>True (A)</p> Signup and view all the answers

Alu RNA is not important for the formation of the nucleolus.

<p>False (B)</p> Signup and view all the answers

What occurs in the G2-phase regarding nucleolar architecture?

<p>Large, fused nucleoli contain poised/inactive rDNA units.</p> Signup and view all the answers

What is the main impact of nucleolar stress on ribosome formation?

<p>It inhibits the formation of ribosomes.</p> Signup and view all the answers

Alu elements represent more than ____% of the human genome.

<p>10</p> Signup and view all the answers

Match the following phases with their key nucleolar characteristics:

<p>G1-phase = Formation of large nucleoli with active transcription units S-phase = RNA Pol I may leave active rRNA genes G2-phase = Presence of poised/inactive rDNA units Nucleolar stress = Significant remodeling due to environmental cues</p> Signup and view all the answers

What happens if cells are treated with amanitin?

<p>Nucleolus dispersal (A)</p> Signup and view all the answers

Under stress, nucleoli maintain their regular size and function.

<p>False (B)</p> Signup and view all the answers

What is the key function of aluRNA in the nucleolus?

<p>To stabilize and form the nucleolus by binding proteins.</p> Signup and view all the answers

What is the primary function of the p53 protein when activated?

<p>Induce apoptosis and DNA repair (A)</p> Signup and view all the answers

The interaction of p53 with MDM2 leads to an increase in p53 levels within the cell.

<p>False (B)</p> Signup and view all the answers

What role does ATM kinase play in the p53 signaling pathway?

<p>ATM kinase phosphorylates and stabilizes p53 upon stress stimuli.</p> Signup and view all the answers

Nucleolar stress allows ribosomal proteins to be released into the ______ and cytoplasm.

<p>nucleoplasm</p> Signup and view all the answers

What happens to ribosomal proteins during nucleolar stress?

<p>They are released and can bind MDM2 (B)</p> Signup and view all the answers

The binding of MDM2 to nucleolar proteins decreases the availability of p53.

<p>True (A)</p> Signup and view all the answers

Name one nucleolar protein that can bind MDM2 and release p53.

<p>p14ARF</p> Signup and view all the answers

Flashcards

Nucleolus

A prominent structure within the nucleus responsible for ribosome biogenesis, where rRNA synthesis and assembly of ribosomal subunits take place.

Fibrillar Center (FC)

The subcompartment of the nucleolus where rRNA synthesis occurs, containing DNA sequences for rRNA, RNA polymerase I, and UBF.

Dense Fibrillar Component (DFC)

The subcompartment of the nucleolus where pre-rRNA transcripts undergo chemical modifications, containing snoRNAs and snoRNP proteins like Fibrillarin.

Granular Component (GC)

The subcompartment of the nucleolus where ribosomal subunits are assembled and mature, containing NPM1.

Signup and view all the flashcards

rRNA (Ribosomal RNA)

The most abundant type of RNA in cells, forming the structural and functional core of ribosomes.

Signup and view all the flashcards

Ribosome

A complex cellular machine composed of rRNA and proteins, responsible for protein synthesis by translating mRNA into polypeptide chains.

Signup and view all the flashcards

Large Subunit (60S)

One of the two subunits that make up a ribosome, containing 3 rRNAs (28S, 5.8S, and 5S) and 47 proteins.

Signup and view all the flashcards

Small Subunit (40S)

One of the two subunits that make up a ribosome, containing a single rRNA (18S) and 33 proteins.

Signup and view all the flashcards

Nuclear bodies

Distinct, often spherical structures within the nucleus, concentrated with specific proteins and RNAs, forming specific regions in the nucleus.

Signup and view all the flashcards

What does the nucleus contain?

The nucleus contains DNA, which is organized into regions of varying condensation called euchromatin and heterochromatin. It also contains nuclear bodies.

Signup and view all the flashcards

Ribosome biogenesis

The process of creating ribosomes, involving the transcription of pre-rRNA, processing of pre-rRNA, and assembly of ribosomal subunits.

Signup and view all the flashcards

What are the types of nuclear bodies?

Nuclear bodies include Cajal bodies, clastosomes, histone locus bodies, nuclear speckles, nucleoli, paraspeckles, perinucleolar compartments, PML-nuclear bodies, and Polycomb bodies.

Signup and view all the flashcards

How do nuclear bodies form?

Nuclear bodies form due to the high concentration of specific proteins and RNA molecules in particular regions of the nucleus.

Signup and view all the flashcards

What is the function of nucleoli?

Nucleoli are responsible for the synthesis of ribosomes, which are essential for protein synthesis, and also play a role in cellular stress responses.

Signup and view all the flashcards

Detention Center

A large subnucleolar structure formed during nucleolar stress. It occupies the central part of inactive nucleoli, leading to the redistribution of nucleolar factors and movement of FC/DFC structures towards the nucleolar periphery.

Signup and view all the flashcards

Nucleolar Stress Response

A cellular response to stress conditions that affects the nucleolus, leading to the inhibition of ribosome biogenesis and the redistribution of nucleolar factors.

Signup and view all the flashcards

p53

A key transcription factor involved in nucleolar stress responses. It controls processes like apoptosis, cell cycle regulation, DNA replication and repair.

Signup and view all the flashcards

MDM2

A protein that inhibits the activity of p53 by promoting its degradation.

Signup and view all the flashcards

TP53 Gene

The gene that encodes the p53 protein, the most frequently mutated gene in human cancer.

Signup and view all the flashcards

p53 Functional Domains

The p53 protein has several functional domains, including transactivation domains, a DNA binding domain, an oligomerization domain, and a C-terminal domain.

Signup and view all the flashcards

How does p53 affect cancer?

Mutations in the TP53 gene can disrupt the tumor-suppressive function of p53, contributing to cancer development.

Signup and view all the flashcards

What is the role of the nucleolus?

The nucleolus plays a crucial role in ribosome biogenesis and acts as a hub for cellular stress responses.

Signup and view all the flashcards

snoRNAs

Small nucleolar RNAs (snoRNAs) are small RNA molecules involved in processing ribosomal RNA (rRNA). They guide modifications like methylation and pseudouridylation of rRNA.

Signup and view all the flashcards

Box C+D snoRNAs

A type of snoRNA that associates with the enzyme fibrillarin, which adds methyl groups to rRNA.

Signup and view all the flashcards

Box H+ACA snoRNAs

A type of snoRNA that associates with the enzyme dyskerin, which converts uridine to pseudouridine in rRNA.

Signup and view all the flashcards

Pre-90S complex

The precursor complex formed during ribosome biogenesis, containing nascent pre-rRNA, ribosomal proteins, and snoRNAs.

Signup and view all the flashcards

Pre-60S and Pre-40S subunits

Products of the Pre-90S complex cleavage, which are further processed to become the large (60S) and small (40S) ribosomal subunits.

Signup and view all the flashcards

Nucleolus Organizer Regions (NORs)

Clusters of ribosomal DNA (rDNA) genes on chromosomes that are the sites of rRNA transcription and ribosome assembly.

Signup and view all the flashcards

Cell cycle-dependent nucleolar dynamics

Nucleoli change their structure and function during the cell cycle, disassembling in mitosis and reforming after cell division.

Signup and view all the flashcards

Nucleolar Association in G1

During the G1 phase, active transcription units of ribosomal RNA genes (rDNA) gather and bind to form large, fused nucleoli. This process is called nucleolar association. All active NORs (nucleolar organizer regions) are contained within these nucleoli.

Signup and view all the flashcards

RNA Polymerase I in S-phase

In the S-phase, RNA polymerase I temporarily detaches from active rRNA genes to prevent collisions with the DNA replication machinery. This leads to the disappearance of the FC (fibrillar center).

Signup and view all the flashcards

Nucleolar Stress

Environmental stress, such as heat shock or acidosis, triggers changes in nucleolar structure and function. A specific intergenic spacer (IGS) RNA is expressed under stress, affecting nucleolar protein activity.

Signup and view all the flashcards

AluRNAs' Role in Nucleoli

AluRNAs are a type of RNA that act as a 'glue' for nucleolar structure. They bind together proteins like nucleolin and nucleophosmin, helping to stabilize the nucleolus.

Signup and view all the flashcards

Amanitin Effect on Nucleoli

Amanitin, a selective inhibitor of RNA polymerase II and III, depletes AluRNA, leading to a dispersed nucleolus. This shows the importance of AluRNAs in maintaining nucleolar structure.

Signup and view all the flashcards

Ribosome Synthesis

The nucleolus is responsible for making ribosomes. Ribosomes play a critical role in protein synthesis.

Signup and view all the flashcards

Nucleolar Function

Nucleoli have a central role in regulating cellular responses to stress. Under stress, their structure and function change significantly.

Signup and view all the flashcards

What is a NOR?

A nucleolar organizer region (NOR) contains the genes for ribosomal RNA (rRNA). It is the site of rRNA transcription.

Signup and view all the flashcards

p53 Role

p53 is a protein that acts as a tumor suppressor, controlling cell growth and preventing uncontrolled division.

Signup and view all the flashcards

MDM2 Interaction

MDM2 is a protein that binds to p53, marking it for degradation and keeping its levels low.

Signup and view all the flashcards

p53 Activation

Stress, like DNA damage, activates p53 by preventing its interaction with MDM2 and promoting its phosphorylation.

Signup and view all the flashcards

Ribosomal Proteins (RPs) and rRNA

RPs and ribosomal RNA (rRNA) are components of ribosomes, essential for protein synthesis.

Signup and view all the flashcards

p53 Target Genes

Activated p53 triggers genes that control cell cycle arrest, DNA repair, or apoptosis.

Signup and view all the flashcards

P14ARF Role

p14ARF is a protein that can bind to MDM2, preventing it from degrading p53.

Signup and view all the flashcards

ATM Kinase

ATM kinase phosphorylates p53, making it active and stabilizing it.

Signup and view all the flashcards

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

Studying That Suits You

Use AI to generate personalized quizzes and flashcards to suit your learning preferences.

Quiz Team

Related Documents

Nucleolar Stress - Unit 13 - PDF

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.

More Like This

Chromosomal Landmarks Quiz
10 questions

Chromosomal Landmarks Quiz

EasedBiedermeier avatar
EasedBiedermeier
Pearson Chemistry Nuclear Chemistry Chapter 25
36 questions

Pearson Chemistry Nuclear Chemistry Chapter 25

TalentedFantasy1640 avatar
TalentedFantasy1640
Nuclear Gauge Safety Certification Course
77 questions

Nuclear Gauge Safety Certification Quiz & Flashcards

ExceedingSodalite avatar
ExceedingSodalite
Nuclear Emission and Decay Quiz
27 questions

Nuclear Emission and Decay Quiz

TopComputerArt avatar
TopComputerArt
Use Quizgecko on...
Browser
Open
Browser
Browser