Mid 2: Lec 11 Flashcards
(9 cards)
4 styles of mirna regulation
The basic approach:
single microRNA–mRNA
Interactions
Broad effects: one
microRNA to many mRNAs
The functional approach
to regulation
The pathway-based
approach to regulation
miR-372 and miR-373
Following Hippo signalling , large tumour
suppressor (LATS) phosphorylates and inhibits YAP and TAZ; this is prevented by high levels of miR-372 and miR-373, which target LATS
miR 125b
example of a miRNA operating as a primary mediator of default repression.
In a normal cell miR-125b targets residual p53 activity, avoiding apoptosis. Following
genotoxic inputs p53 is activated and miR-125b is repressed, inducing apoptosis.
let-7 miRNA differentiation
example of microRNAs and signaling gradients
let-7 expression increases during differentiation, resulting in
progressive inhibition of RAS signalling. This enables self-renewal in progenitor cells but restrains it while cells differentiate.
miRNAs in bistable fate choices
n a cell, a transcription factor
(TF) inhibits the expression of a miRNA; in turn, the miRNA inhibits expression of the TF. The cell can adopt two alternative
fates: state A is the default fate, in which miRNA expression dominates and the expression of the TF is turned off. In state B,
an extrinsic cue (signal) stabilizes the TF, promoting cell differentiation and leading to repression of the miRNA and give a
different cellular outcome
microRNAs and cancer
oncogenes or tumor suppressors
miR 21
oncogenic miRNA
Restoring microRNA levels as cancer treatment inc specific mirna
synthetic oligonucleotides to mimic miR-34
reduces tumor growth
blocking mi rna as therapy
antisense oligonucleotides