Sub-nuclear bodies

Question 1

What are sub-nuclear structures?

Answer 1

Discrete localisations within the nucleus

Question 2

What is the nucleolus?

Answer 2

• composed of proteins & nucleic acids
• FC, DFC, GC
• ribosome biogenesis

Question 3

How is the nucleolus formed?

Answer 3

• formed around NORs (tandem repeats of rRNA genes)

Question 4

What are the roles of the 3 compartments of the nucleolus?

Answer 4

• FC - depot of rDNA genes
• DFC - Maturation of pre-mRNA transcripts
• GC - assembly of pre-ribosomal particles

Question 5

What happens during ribosome biogenesis? (not in detail)

Answer 5

• rRNA genes, RNA pol I or II
• long precursor 45S pre-rRNA
• processing to 18S RNA, 5.8S, 5S & 28S RNA molecules
• guide RNAs, snoRNAs, snoRNPs
• maturation 40S and 60S
• exported through NPC

Question 6

What are ribosomopathies?

Answer 6

A range of disorders in which genetic abnormalities cause impaired ribosome biogenesis/function

Question 7

Examples of ribosomopathies?

Answer 7

• Diamond-Blackfan anemia
• Dyskeratosis congenita
• Treacher Collins syndrome (TCS)

Question 8

Why is the nucelolus NOT a steady state structure?

Answer 8

3 types of nucleolar protein

• mainly in nucleus (fibrillarin)
• part time in nucelolus (ribosomal proteins)
• Time/condition dependent

Question 9

How is the nucleolus associated with disease?

Answer 9

morphological changes involving

• change in ribosome biogenesis
• loss of proteins to the nucleolus

Question 10

How can nucleoli be used to detect cancer?

Answer 10

• enlarged, prominent
• high growth rate
• can use a stain and use it as a BIOMARKER

Question 11

what are the 2 links between ribosome and cancer?

Answer 11

• increased ribosome biogenesis

- deficiencies in ribosome function

Question 12

Why do viruses redistribute proteins in or out of the nucleolus?

Answer 12

• utilise nucleolar proteins to enhance virus replication

- subvert anti-viral pathways

Question 13

Why does coronavirus, which replicates in cytoplasm, encode protein localising to the nucleolus?

Answer 13

• sequester nucleolar proteins to enhance translation of viral mRNAs in the cytoplasm

Question 14

What are the reasons for Herpes targeting the nucleolus?

Answer 14

• encodes 8 proteins which localise to nucleolus
• viral proteins localise at different stages
• Dramatic change of nucleolar proteome e.g. RNA processing, DNA synthesis, replication & repair

Question 15

What sub-nuclear structures have splicing related functions?

Answer 15

• Nuclear speckles
• Cajal bodies
• Gems

Question 16

What sub-nuclear structure has transcriptional repression?

Answer 16

• PcG Bodies

Question 17

What sub-nuclear structure has protein complex assembly/modification?

Answer 17

• PML Bodies

Question 18

What does the spliceosome consist of?

Answer 18

U1, U2, U4, U5, U6 snRNPs

approx. 125 proteins

Question 19

What do cajal bodies (3-5 per cell) contain?

Answer 19

proteins that participate in biogenesis of mRNA

involved in maturation & assembly of snRNPs

Question 20

What do nuclear gems contain?

Answer 20

• do NOT contain snRNPs
• contain SMN protein
• assist CBs in snRNP biogenesis

Question 21

What is Spinal Muscular Atrophy?

Answer 21

• defect in SMN1 gene (essential for snRNP assembly)
• death of neuronal cells spinal cord
• muscle atrophy

Question 22

What are nuclear speckles?

Answer 22

• enriched in pre-mRNA splicing factors
• irregular
• dynamic, components can cycle

Question 23

What is the function of nuclear speckles?

Answer 23

• storage and modification for pre-mRNA splicing factors, including snRNPs
• CLOSE to ACTIVE GENES - enhance metabolic activity in mRNA maturation & export
• euchromatin

Question 24

What is retinitis pigmentosa?

Answer 24

• mutation in splicing factor
• night blindness > tunnel > blind
• linked to splicing factor PRP31

Question 25

What are Polycomb bodies?

Answer 25

CONTRAST to speckles

• gene repression
• associated with heterochromatin
• induce epigenetic silencing
• recruit complex, modify chromatin
• overexpression - cancer

Question 26

What are PML bodies?

Answer 26

• promiscuous, diverse function
• favour sequesteration/release of proteins, post-trans mods
• respond to cellular stress

Question 27

How do PML bodies form?

Answer 27

• dimerize, multimerize
• sumoylation - spherical
• SIM-containing, sumoylaed partners - recruited by SUMO into inner core

Question 28

How is acute promyelocytic leukaemia caused by PML body mutations?

Answer 28

• forms reciprocal translocation within RARalpha genes
• loss of PML bodies
• hybrid altered protein
• binds & blocks transcription & differentiation
• accumulate immature granulocytes

Question 29

What is the role of PML bodies?

Answer 29

3 main groups

• nuclear storage for accumulated proteins
• catalytic surfaces to be post-trans mod
• active sites for e.g. chromatin regulation

Question 30

How are PML bodies involved in apoptosis & senescence?

Answer 30

• regulate p53- dependent apoptotic & cellular senescence pathways induced by stress
• recruits cell proteins to PML bodies - post trans mods, activate p53
• inhibit MDM2

Question 31

How are PML bodies involved in virus infection?

Answer 31

targeted by viruses to:

1) viruses do not want PML bodies to initiate host response against virus
2) release proteins within PML body - enhance virus replication