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Cell Bio > Nucleolar Stress > Flashcards

Nucleolar Stress Flashcards

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Biology 101 flashcards
1
Q

What is the nucleus

A

Large organelle in eukayrotic cells that contains DNA organize into regions with different condensation

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2
Q

What is the nucleus encolosed by

A

A double membrane the nuclear envelope

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3
Q

What are nuclear bodies

A

Regions with high concentration of specific proteins and RNA that form distinct often roughly spherical structures within the nucleus

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4
Q

What is one type of nucleor body we know

A

HSF1and HSF2

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5
Q

Can a nucleus contain several nucleoli

A

YES

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6
Q

What are nucleoli responsible for

A

Ribosome biogenesis in cells and regulating cellular stress responses

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7
Q

What are the three steps of biogenesis of ribosomes

A
  1. Transcription of pre-rRNA
  2. Processiong of pre-rRNA
  3. Assembly of ribosome subunits
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8
Q

What are the three different nucleolus sub compartments

A

Fibrillar center
Dense fibrillar component
Granular components

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9
Q

What is the fibrillar center

A

Ribosomal RNA synthesis occurs it associated with DNA sequences that encodes for rRNA, RNA polymerase 1 machinery and UBF

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10
Q

What is UBF

A

Upstream binding factor is an essential component of the RNA pol 1 preinitation compelex

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11
Q

What is the dense fibrialr component

A

Contains nascent pre-rRNA transcripts pre-rRNA processing factors including snoRNAs and snoRNP proteins e.g. Fibrillarin and Nop58 The pre-RNA precursor undergoes chemical modifications here

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12
Q

What is the granular component

A

Contains ribosomal subunits in various stages of assembly a specific protein here is NPM1. Precursor ribosomal subunits are ready to be sent to the cytoplasm.

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13
Q

What is the nucleophosmin

A

Nuclear export chaperone and directs the nuclear export and directs the nuclear exoprt of the 40S and 60 S ribosomal subunits

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14
Q

What is the most RNA in cells and what comes after that

A

rRNA then tRNA and then mRNA and non coding RNA

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15
Q

How many subunits is a eukaryotic composed of

A

4 different rRNA molecules organized into a large subunit and small subunit

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16
Q

What does the small subunit consint of

A

Single rRNA 18s which is 33 proteins

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17
Q

What is large ribosomal consits of

A

(60S) 3 rRNAS (28s, 5.8s and 5s) assembled ribsome is 80s

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18
Q

What is pre-rRNA

A

A single transcription unit which encodes 18S 5.8S and 28S rRNA

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19
Q

What is the order of pre-RNA and what are the differences between species

A

always in the 5’-3’ order going from 18s 5.8S and 28S only thing that is different between species are the size of the sapcers in the pre-rRNA transcript

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20
Q

How are pre-rRNA genes arranged and fuction as waht

A

Tandem arrays sitting one by one beside each other and function as nucleolar organize which is where the nucleolus is localized

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21
Q

Where are the 56.8S,18S and 28S clustered

A

5 different human chromsomes 13,14,15,21,22

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22
Q

What is the transcription of pre-rRNA mediated by

A

RNA polymerase 1

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23
Q

Where is 5s rRNA gene

A

Present as a single tandem on chromsome 1 and the transcription occurs in the nucleoplasm using RNA Polymerase 3

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24
Q

How many rRNAs are there in primary rRNA

A

3

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25
Q

How is the 3 split up

A

Methylation and pseudouridination of pre-rRNA which requires small nucleolar RNAS they hybridize to pre-rRNAs and bind enzymes that are responsible for the modification

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26
Q

What are snoRNA

A

Have a stem loop structure and associate with specific proteins to form small nucleolar ribonucleoproteins

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27
Q

What are the two major classes of snoRNAS

A

Box C+D and box H+ACA

28
Q

What does box C+D associate with

A

methyl transferase fibriallarin which mediates methylation of specific riboses

29
Q

What does H+ACA snoRNA assocaite with

A

Pseudorudine syntahse dyskerin which converts uridine to pseudorudine invovles rotation of the pyrimidine ring

30
Q

What are the steps of ribosomal subunit assembly

A
  1. Specific ribosomal proteins and snoRNAs associate with the nascent pre-rRNA transcript and form precursor Pre-90s complex in nucleolus
  2. Pre-90s complex is cleaved into two prescursor subunits Pre-60s and Pre40s
  3. Both small and large subunits pass through nuclear pore complex and move to cytoplasm where mature and functional ribsomes are assembled
31
Q

Does it require a lot of energy

A

GTPases and ATPases espically with the large subunit

32
Q

Where are nucleoli formed

A

Clusters of ribosmal genes called Nucleolus Organizer Regions NORs

33
Q

What are nucleoli

A

Dynamic structures: each mitosis nucleolus breaks up as a chromsomes condense and after mitosis nucleous reformes at the tips of several chromsomes

34
Q

Where are these culsters

A

Usually on the short arm of chromsomes which contains genomic repeats/transcription units encoding rRNA

35
Q

What happens during the M phase

A

nucleolus dissasembles and many nucleolar proteins associate with the surface

36
Q

What remains associated with active rDNA during M-phase

A

UBF serving as a miotic bookmark and binding platform for the RNA Pol 1 machinery

37
Q

What happens in G1 phase

A

FC/DFC/DC structures evolve around active transcrption units resulting in the formation of a few large nucleoli

38
Q

What happens in S-phase

A

RNA pol 1 leave active rRNA genes to prevent collisions with replication machinerany leads to dissapperance of FC cells focus energy on synthesizing molecules for S-phase they do not want to make new ribosmes

39
Q

What happens in G2 phase

A

Large fused nucleoli may contain poised/inactive rDNA units genes are duplicated but not all of them are active in preparation for mitosis

40
Q

the formation of nucleolus depend on and where are they encoded

A

specefic types of RNA called aluRNA (glue to the nucleoli) encoded in the introns

41
Q

What is the most abundant repetitive intronic elements

A

Alu repeats scattered throughout the human genome at sites where their insertion has not disrupted gene experession

42
Q

What are alu transcrips synthesize by

A

RNA pol 2 and 3

43
Q

What does aluRNA do

A

Stabiliz and form the nucleolus by binding together the proteins which make the nucleolus (nucleolin and nucleophosmin)

44
Q

What happens if you treat cells with amanitin

A

It is a selective inhibitor of RNA pol 2 and 3 and induce the depletion of aluRNA dispersed nucelolus

45
Q

Under normal conditions what is happening

A

There is a regular transcription activity and the nucleoli are doin their regular job making ribosomes

46
Q

What happens under stress condtions

A

Signficant remodeling of nucleoli

47
Q

What do environmental cues such as heat shock do

A

Induce expression of specific intergentic spacer which targets proteins containing a peptide code termed the nucleolar detentions sequence

48
Q

What happens when there is an accumulation of IGS

A

Formation of a large subnucleolar structure termed detention center structural remodeling and transcriptional inactivation of nucleoli

49
Q

What is the detention center

A

Central part of inactive nucleoli which leads to redistribution of nucleolar factors and movement of FC/DFC structures towards nuclolar periphery there is a relocalzation of proteins in the nucelolus under stress inhibit formation of ribosmes

50
Q

What is the compostion of protiens in the nucleoli

A

30% ribsomes subunit biogenesis
70% are not releated to biogenesis but are important in regulating different aspects of stress singaling

51
Q

What is the nucleolus being recognizes as

A

Key hub in cellular stress response by senesing and recating to various stimuli

52
Q

What does nucleolar stress signaling pathway rely on

A

Dynamic binding and release of proteins in response to stress timuli

53
Q

What is P53 known as

A

Transcription factor as the tumour suppressor gene or the guardian of genome

54
Q

What are the domains of P53

A
  1. Two transactivation domains at the N-termins
  2. DNA binding domain
  3. Oligomerization domain resosible for tetramerization of p53
  4. C-terminal domian with nuclear export and nuclear localization signals
55
Q

What is P53 inihibited by

A

MDM2 induces its degradation

56
Q

What is the active form of p53

A

Tetramer

57
Q

What is most frequently mutated gene in human cancer and in which domain

A

TP53 and DNA-binding domain

58
Q

Why is p53 is low in normal conditions

A

Because of E3 ubiquitin ligase MDM2 and fast degradation in proteasomes

59
Q

What is the P53 signaling pathway under stress conditions

A

DNA damage activates ATM kinase that phosphorylates p53 to stabalize it and MDM2
Once phosphorylated p53 tetramer bind response elements in p53 induced genes

60
Q

What can p53 do once activated

A

Induce apoptosis stop cell divsion so cell have energy (maintain in G1 and G2) and induce DNA repair

61
Q

What is another nucleor protein that can bind MDM2

A

p14ARF

62
Q

What is happening in the nucelolus under normal growth conditions

A

Ribosomal DNA repeats are transcribed by RNA pol 1 making rRNA
Production of RP which interact with rRNAS into large and small subunits
Then released to nucleus into cytoplasm

63
Q

Where is p53 translated under normal conditions

A

In the cytoplasm then goes into the nucleus where it interacts with MDM2 gets ubquiniated and then degraded back into the cytoplasm

64
Q

What happens to the nucelolus under stress response

A

Ribosomal protiens and rRNAS are released from the nucelolus into the nucleoplasm and cytoplasm

65
Q

What happens to the membrane of the nucelouls

A

Dissasembly all of the protiens present in the nucelous are not going to make any more ribosomal subunits now they do other jobs and have a high affinity to bind MDM2

66
Q

What happens to MDM2 under stress

A

Binds to ribsome portiens and result in relase of p53 which is available now to be phosphorylated and induces the activation of p53 target genes

67
Q

What does RPL26 do

A

Binds p53 mRNA and enhances its translation increasing the levels of p53 in cells

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