Precursor miRNA loop-modulated target regulation

摘要

Modulation of mRNA activity is achieved with precursor miRNAs (ta-RNAs). ta-RNAs, primarily pre-miRNAs and pri-miRNAs, including truncated and mutated ta-RNAs, are employed for modulation of mRNA expression where it is found that pri- and pre-miRNA have activity independently of the presence of functional mature miRNAs. Modification of at least one of the stem and loop of the ta-RNAs to enhance binding of the ta-RNA to the target mRNA is employed. The modification may be enhanced complementarity between the ta-RNA and the target mRNA and/or improved thermodynamic efficiency in binding of the ta-RNA to the target.

主权项

1. A composition comprising:
a mutated precursor miRNA that hybridizes to a separate target mRNA, wherein said mutated precursor miRNA is from a wild-type precursor miRNA that hybridizes with said separate target mRNA sequence and which has an wild-type terminal loop comprising a wild-type terminal loop sequence, and wherein said mutated precursor miRNA comprises a stem sequence and a terminal loop, wherein said terminal loop comprises a mutated terminal loop sequence with the same length as said wild-type terminal loop sequence, wherein at least the first and second nucleotides, and/or the seventh and eighth nucleotides, counting from the 5′ end of said mutated terminal loop sequence, are substituted to enhance or reduce activity of said mutated precursor miRNA in binding and repressing said target mRNA sequence as compared to said wild-type precursor miRNA.