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EXMD 504 > microrna > Flashcards

microrna Flashcards

1
Q

who discovered microrna

A

ambros and lee

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2
Q

what was used to discover microrna

A

c elegans

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3
Q

what was the main discovery that led to the discovery of mirna

A

the c elegans heterochronic gene lin-4 encodes small rna with antisense complementarity to lin 14

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4
Q

what is ma161

A

it is a mirna that was found when they discovered mirna

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5
Q

true or false: lin-4 is a repressor of lin-14

A

true

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6
Q

what are the two lin-4’s

A

-lin-4L
- lin-4S

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7
Q

what are the quirks of the two lin-4’s

A

-4L BPs with itself
-4S is the mature one

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8
Q

where do the lin-4 and lin-14 bp

A

at the 3’ end and the 5’ end

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9
Q

true or false: micrornas are conserved

A

true

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10
Q

what do micrornas do

A

they control genes

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11
Q

how many loci encode let-7 microrna

A

4 loci

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12
Q

how many micrornas are in the human genome

A

2000

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13
Q

what happens to c elegans let7 mutants?

A

they keep dividing and fail to differenciate

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14
Q

true or false: let7 and mir-84 are very similar

A

so true they are so similar that let 7 sites are also potential mir84 binding sites

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15
Q

true or false: there is a relationship between pten and let7

A

false it is between let 7 and ras

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16
Q

what does let7 control

A

it controls the expression in ras
-basically it shuts down ras

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17
Q

true or false: in tumor tissues there is high ras and low let 7

A

true

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18
Q

what does let7 do in c elegans

A

it controls the developmental timing

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19
Q

where are located human micrornas usually

A

at fragile sites and genomic regions involved in cancer

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20
Q

true or false: micrornas are usually tumor supressor

A

true

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21
Q

name a tumor activator microrna

A

the mir-17-92
it is amplified in cancers

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22
Q

in which cancer is mir1792 over expressed

A

lymphomas like burkitts lymphomas

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23
Q

the mir1972 cluster collaborates with what

A

c-myc, it is associated with poor outcome

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24
Q

how many clusters does mir1972 encode

A

6 clusters

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25
Q

microrna is transcribed by what

A

rns pol 2

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26
Q

what is primirna

A

-pre mature micro rna, thereare multiple conformation of primary transcript
-it associated with drosha

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27
Q

what does drosha do

A

it cleaves smth on the pri-mirna and then it becomes pre-mirna

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28
Q

what does the pre-mirna associate with? and what happens after

A

-dicer and trbp and dicer cleaves the precursor
-the rna then binds to argonaute and it then cleaves one strand

29
Q

what happens after argonaute cleaves the rna strand

A

-it binds with gw182
-this makes the mirisc
-it lookjs around becayse it is like a transcriptome and then it will try to find targets

30
Q

which sections of the argonaute is very conserved

A

paz and MID

31
Q

where do messenger rna bind to on argonaute

A

on the MID cleft

32
Q

what is PIWI and where is it found

A

-found on argonaute
-looks like rnaseH (cleaves mrna, microrna hybrids)
-rnase H basically cleavage activity
-piwi is removed unless there is perfect bp between microrna and mrna

33
Q

true or false: there are only a little bit of interactions with argonaute and microrna

A

false: there are a lot of different interactions

34
Q

true or false: argonaute binds mature, single stranded 2Int siRNAs and mirna

A

true

35
Q

the 5’ phosphate of argonaute is bound by what

A

mid domain

36
Q

the 3’ end of argonaute is bound by what

A

paz domain

37
Q

when does the piwi domain fold

A

-iyt folds as an rnaseH domain and carries out the slicer activity and then it scans the rna in the cell for complementarity

38
Q

true or false: in the vast majority of mrna targets incompletely bp with mirnas

A

true

39
Q

mechanisms of mirna mediated silencing

A

-on the 3’ end there is ccr4-not and it represses things

40
Q

what are processing bodies

A

they are regions within the cytoplasm of the eukaryotic cekk consisting if many enzymes involved in mrna turnover

41
Q

p bodies are likely one of the sites of what?

A

-microrna action as mirna targeted mrnas are recruited to p bodies and destabilized or sequestrered from translational machinery

42
Q

the following activities of p bodies were associated but not yet directly demonbstrated

A

-decapping and degradation of mrna
-storing mrna until needed for translation
-aid in translational repression by mirns

43
Q

what is a polycistron

A

a huge cluster of microrna

44
Q

can you use micrna for cancer detection

A

-microrna expression profiling using microarrays
-varies with cells fate and staye
-can use this to identify the cells origin
-can use it to discover new cancer types

45
Q

what does hsa mir 155 high expression predict

A

-low patient survival aka suggest oncogeneity

46
Q

what does hsa let7a high expression predict

A

higher patient survival

47
Q

what is a heatmap

A

A heat map is a data visualization technique that represents the magnitude of a phenomenon as color in two dimensions. It is commonly used to visualize the distribution of data across a surface or within a dataset. The term “heat map” is derived from the use of colors to represent intensity, with warmer colors (such as red or yellow) indicating higher values and cooler colors (such as blue or green) indicating lower values

48
Q

what does mir1792 2

A

IT MITIGATES PROGRAMMED cell death and is a predictor of treatability

49
Q

true or false: mic overexpressed is usually cancer time

A

true

50
Q

true or false: high 1972 predicts bad patient outcome

A

true

51
Q

true or false: when you KO pten you die

A

so true bestie

52
Q

what dies BIM do

A

it regulates apoptosis

53
Q

true or false: when you overexpress mir1892 you get more apoptosis

A

true

54
Q

lymphoproliferative disease and autoimmunity in mice with….. mir 1792 expression in lymphocytes

A

increased

55
Q

what is synthetic lethality

A

it occurs when two otherwise non lethal mutations together result in an inviable cell

56
Q

synthetic lethal genes are informative of what?

A

sensitive points of within a specific tumor type, and become strong candidates for drug targeting as the same drugs should not affect the normal cells

57
Q

true or false: mir1792 can cause tumor addiction

A

true

58
Q

synthetic lethality between rb, p53 and dicer or mir1972 in retinal progenitors supresses what

A

retinoblastoma formation

59
Q

what happens when you ko rb and p53 in cancer cells

A

you get less retinoblastoma

60
Q

true or false: mir1792 and dicer have the same effect

A

true they have the same effect

61
Q

true or false: mir1792 is required for mouse retinoblastoma devlopment

A

true

62
Q

RNAi and microRNA –oriented therapy in cancer:
rationales, promises, and challenges

A
  • De novo rnai programming using synthetic sirnas to
    target the expression of genes
  • Strengthening or recapitulation of the physiologic
    targeting of messenger rnas by specific mirnas
  • Sequence-specific inhibition of mi rna functions by
    nucleic acid analog
63
Q

true or false: cancer tweaks gene structure to dodge microrna regulation

A

true

64
Q

what does cancer do to to skip microrna binding sites

A

3’ utr shortening and alternatibe polyadenylation
-when cells proliferate there is less polyadenylation

65
Q

true or false: 3’ utr are longer in differenciated cells

A

true they are shorter when they are shorter in cancer

66
Q

true or false: when you lose microrna you have more proliferation

A

true

67
Q

what caused the 3’ utr shortening

A

alternative polyadenylation

68
Q

several types of cancer downregulate microrna, which ones

A

sarcomas and several metastatic cancers
-sometimes associated with a loss or mutation in the microrna biogenesis machinery such as dicer

69
Q
A

EXMD 504 (12 decks)

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