miRNA
Large class of non-coding RNAs regulating many biological processes in animals, plants, and viruses. They exert their regulatory role by modulation of gene expression through degradation of mRNA or suppression of protein synthesis
Responsible for posttranscriptional modulation of gene expression.
Synthesis
- MiRNA genes are transcribed into primary RNA transcript (pri-miR)
- Stem loop structure undergoes processing in nucleus to form ~70nt long intermediate termed precursor miRNA (pre-miR)
- Performed by microprocessor complex comprising RNAse III Drosha and double-stranded RNA-binding protein, DiGeorge syndrome critical region gene 8 (DGCR8).
- pre-miRs are transported into cytoplasm through nuclear pores by Exportin-5 complex
- Further processing by RNAse III Dicer & associated trans-activation response RNA binding protein (TRBP) to yield double stranded RNAs 18-24 nt in length
- Double stranded RNAs are unwound and mature single-stranded miRNA is incorporated into argonaute protein-containing RNA-induced silencing complex (RISC)
- miRNA functions as a template for homology directed mRNA targeting of 3’ untranslated region (UTR)
Schematic of miRNA biogenesis pathway and function. MicroRNA (miRNA) is initially transcribed by RNA pol II transcription factor and form a hairpin structure termed pri-miRs. Then Drosha and DGCR8 complex cleave the molecule producing pre-miRs in the nucleus. Exportin-5 transfers the double strand miRNA into the cytoplasm where miRNA undergo further editing by TRBP and Dicer complex to form miRNA duplex, which are eventually unwound to reveal the mature miRNA. MiRNA interact within a RISC complex and provide guidance for targeting mRNAs for degradation or translational repression.
Regulation
- MiRNAs can posttranscriptionally regulate large number of genes by mRNA degradation or translational inhibition.
- MiRNAs can bind to their target 3’ UTRs despite mismatched pairing → enables miRNA to regulate hundreds of mRNA targets
- Multiple miRNA can regulate a single gene
- MiRNAs regulate expression of up to 80% of genes in humans, including cellular functions such as development, cell proliferation, differentiation, apoptosis, signal transduction, and cell cycle.