MicroRNAs Flashcards
How are miRs synthesised ?
Transcribed as primary miRs by RNA Pol2
Hairpin structure cleaved by a microprocessor complex containing Drosha and Pasha releasing a 70-75 nucleotide precursor
Exported to the cytoplasm via exportin5
Fixer ribonuclease produces 22-23bp duplex
Duplex unwound to release mature miRNA and passenger miRNA (usually degraded)
The genes for them can be found on their own eg. miR-21, in clusters eg. miR17-92 or in the introns of other genes eg. miR155
How do miRs control gene transcription?
Loaded onto the Argonaute protein (Ago), a component of the RNA-induced silencing complex (RISC)
Binds to the 3’UTR of target mRNA through base pair complementarity
RISC either represses translation or induces destruction
Occurs in discrete cytoplasmic bodies called P bodies which are sites of RNA degradation
Repressed translation at the initiation or the elongation stage
Promotes degradation by promoting decapping and deadenylation
Describe miR sequence complementarity
Look for conserved sequences between species
Some mRNAs will have many miRs and some miRs will have many target mRNAs
Describe tumour suppressor miRs
miR34 targets CDK4+6, Cyclin D/E and Bcl2, causing apoptosis and cell arrest. Lost in many solid organ cancers. Induced by p53.
Overexpression of myc leads to overexpression of the miR17-92 cluster which contributes to cancer formation. As a result there is increased proliferation, blocking of apoptosis and inducing of angiogenesis.
Describe oncogenic miRs
mir221 targets p27 in liver and thyroid cancers
mir17-92 cluster targets E2F1, Bim ⬆️lymphomas and solid organ cancers
How can miRs be used in cancer therapies?
Inhibitors eg. Sponges for excess oncomirs
Mimic miRs for a loss of anti-oncomirs
What are miRNAs?
Large family of single strand, non-coding, 20-22 nucleotide long RNAs
Conserved
Correlation with complexity of organism
Down regulate gene transcription
