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
Perfect in plant
Imperfect in humans
5’ proximal bases 2-7 is the seed- perfect
Look for conserved sequences between species
Some mRNAs will have many miRs and some miRs will have many target mRNAs
Describe tumour suppressor miRs
miR15 and miR16 target bcl2 in lost in chronic lymphocytic leukaemia, multiple myeloma and prostate
let7 target Ras lost in lung and breast cancer
miR34 targets CDK4+6 and Cyclin D and E lost in many solid organ cancers
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
