microRNA-122 (miR-122)
Liver-specific microRNA of about 22 nucleotides that is the most abundant miRNA of adult liver. Because it is absent from the other mouse tissues analyzed and from 293 cells, perfectly complementary miR-122 target sites in a transgene 3′ UTR (miR-122ts) silence expression in hepatocytes while leaving other tissues unaffected.
Origin: Mammalian liver; derived from the noncoding hcr transcript
Characteristics
Variants of miR-122 account for 72% of all miRNAs cloned from adult mouse liver, and miR-122 is undetected in the other mouse tissues analyzed. The stored mature strand is the 23-nucleotide miR-122a as cloned; miR-122b and the shared 22-nucleotide core differ only at the 3′ terminus. Against perfectly complementary target sites it directs mRNA degradation: five copies of miR-122ts lowered a transgene mRNA 96% in mouse liver.
Applications: Endogenous effector for miR-122ts-based liver detargeting of AAV vectors: five target copies in AAV9 cassettes cut mouse liver luciferase about 50-fold and LacZ about 70-fold after intravenous injection without lowering skeletal muscle expression.
Limitations: Acts only in miR-122-expressing hepatocytes, so it cannot restrict expression in other tissues: miR-122ts left tibialis anterior and 293 cells unchanged and raised cardiac expression slightly in AAV9-treated mice. It removes liver expression but does not itself drive expression in a target tissue.
Mature sequence
References
- Lagos-Quintana et al. (2002). Identification of tissue-specific microRNAs from mouse. Curr Biol - Lagos-Quintana 2002 Tissue miRNAs
- Qiao et al. (2010). Liver-specific microRNA-122 target sequences incorporated in AAV vectors efficiently inhibits transgene expression in the liver. Gene Ther - Qiao 2010 miR-122T AAV