microrna Flashcards
who discovered microrna
ambros and lee
what was used to discover microrna
c elegans
what was the main discovery that led to the discovery of mirna
the c elegans heterochronic gene lin-4 encodes small rna with antisense complementarity to lin 14
what is ma161
it is a mirna that was found when they discovered mirna
true or false: lin-4 is a repressor of lin-14
true
what are the two lin-4’s
-lin-4L
- lin-4S
what are the quirks of the two lin-4’s
-4L BPs with itself
-4S is the mature one
where do the lin-4 and lin-14 bp
at the 3’ end and the 5’ end
true or false: micrornas are conserved
true
what do micrornas do
they control genes
how many loci encode let-7 microrna
4 loci
how many micrornas are in the human genome
2000
what happens to c elegans let7 mutants?
they keep dividing and fail to differenciate
true or false: let7 and mir-84 are very similar
so true they are so similar that let 7 sites are also potential mir84 binding sites
true or false: there is a relationship between pten and let7
false it is between let 7 and ras
what does let7 control
it controls the expression in ras
-basically it shuts down ras
true or false: in tumor tissues there is high ras and low let 7
true
what does let7 do in c elegans
it controls the developmental timing
where are located human micrornas usually
at fragile sites and genomic regions involved in cancer
true or false: micrornas are usually tumor supressor
true
name a tumor activator microrna
the mir-17-92
it is amplified in cancers
in which cancer is mir1792 over expressed
lymphomas like burkitts lymphomas
the mir1972 cluster collaborates with what
c-myc, it is associated with poor outcome
how many clusters does mir1972 encode
6 clusters
microrna is transcribed by what
rns pol 2
what is primirna
-pre mature micro rna, thereare multiple conformation of primary transcript
-it associated with drosha
what does drosha do
it cleaves smth on the pri-mirna and then it becomes pre-mirna
what does the pre-mirna associate with? and what happens after
-dicer and trbp and dicer cleaves the precursor
-the rna then binds to argonaute and it then cleaves one strand
what happens after argonaute cleaves the rna strand
-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
which sections of the argonaute is very conserved
paz and MID
where do messenger rna bind to on argonaute
on the MID cleft
what is PIWI and where is it found
-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
true or false: there are only a little bit of interactions with argonaute and microrna
false: there are a lot of different interactions
true or false: argonaute binds mature, single stranded 2Int siRNAs and mirna
true
the 5’ phosphate of argonaute is bound by what
mid domain
the 3’ end of argonaute is bound by what
paz domain
when does the piwi domain fold
-iyt folds as an rnaseH domain and carries out the slicer activity and then it scans the rna in the cell for complementarity
true or false: in the vast majority of mrna targets incompletely bp with mirnas
true
mechanisms of mirna mediated silencing
-on the 3’ end there is ccr4-not and it represses things
what are processing bodies
they are regions within the cytoplasm of the eukaryotic cekk consisting if many enzymes involved in mrna turnover
p bodies are likely one of the sites of what?
-microrna action as mirna targeted mrnas are recruited to p bodies and destabilized or sequestrered from translational machinery
the following activities of p bodies were associated but not yet directly demonbstrated
-decapping and degradation of mrna
-storing mrna until needed for translation
-aid in translational repression by mirns
what is a polycistron
a huge cluster of microrna
can you use micrna for cancer detection
-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
what does hsa mir 155 high expression predict
-low patient survival aka suggest oncogeneity
what does hsa let7a high expression predict
higher patient survival
what is a heatmap
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
what does mir1792 2
IT MITIGATES PROGRAMMED cell death and is a predictor of treatability
true or false: mic overexpressed is usually cancer time
true
true or false: high 1972 predicts bad patient outcome
true
true or false: when you KO pten you die
so true bestie
what dies BIM do
it regulates apoptosis
true or false: when you overexpress mir1892 you get more apoptosis
true
lymphoproliferative disease and autoimmunity in mice with….. mir 1792 expression in lymphocytes
increased
what is synthetic lethality
it occurs when two otherwise non lethal mutations together result in an inviable cell
synthetic lethal genes are informative of what?
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
true or false: mir1792 can cause tumor addiction
true
synthetic lethality between rb, p53 and dicer or mir1972 in retinal progenitors supresses what
retinoblastoma formation
what happens when you ko rb and p53 in cancer cells
you get less retinoblastoma
true or false: mir1792 and dicer have the same effect
true they have the same effect
true or false: mir1792 is required for mouse retinoblastoma devlopment
true
RNAi and microRNA –oriented therapy in cancer:
rationales, promises, and challenges
- 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
true or false: cancer tweaks gene structure to dodge microrna regulation
true
what does cancer do to to skip microrna binding sites
3’ utr shortening and alternatibe polyadenylation
-when cells proliferate there is less polyadenylation
true or false: 3’ utr are longer in differenciated cells
true they are shorter when they are shorter in cancer
true or false: when you lose microrna you have more proliferation
true
what caused the 3’ utr shortening
alternative polyadenylation
several types of cancer downregulate microrna, which ones
sarcomas and several metastatic cancers
-sometimes associated with a loss or mutation in the microrna biogenesis machinery such as dicer
