Competitive modulation of microRNAs
The present invention provides compounds and methods for competitive modulation of microRNAs. Such compounds and methods have profound effects on cells. MicroRNAs (microRNAs), are small (approximately 18-24 nucleotides in length), non-coding RNA molecules encoded in the genomes of plants and animals. In certain instances, microRNAs regulate the expression of genes by binding to the 3′-untranslated regions (3′-UTR) of specific mRNAs. More than 1000 different microRNAs have been identified in plants and animals.
1. A method for identifying a competitive microRNA modulating compound comprising:
performing an assay to determine whether a test compound is capable of competing with at least one microRNA for a microRNA-associated protein, wherein the assay comprises measuring the amount and/or activity of at least one microRNA in a cell and at least one object protein in a cell; wherein
if the test compound modulates the amount and/or activity of at least one microRNA in the cell and modulates the amount or activity of protease granzyme B in the cell, then it is a competitive microRNA modulating compound.
2. The method of claim 1 , wherein the microRNA-associated protein is Ago2.
3. The method of claim 1 , wherein the microRNA-associated protein is nucleolin.
4. The method of claim 1 , wherein the microRNA-associated protein is nucleophosmin.
5. The method of claim 1 , wherein the microRNA-associated protein is Rat1p.
6. The method of claim 1 , wherein the microRNA-associated protein is XRN2.
7. The method of claim 1 , wherein the competitive microRNA modulating compound decreases the amount and/or activity of at least one microRNA in the cell.
8. The method of claim 1 , wherein the competitive microRNA modulating compound increases the amount and/or activity of at least one microRNA in the cell.
9. The method of claim 1 , wherein the microRNA modulating compound reduces the amount of α-tubulin in the cell.
10. The method of claim 1 , wherein the test compound is a small molecule.
11. The method of claim 1 , wherein the test compound is an oligomer.
12. The method of claim 1 , wherein the test compound is an oligonucleotide.
13. The method of claim 12 , wherein the oligonucleotide is double-stranded.
14. The method of claim 12 , wherein the oligonucleotide is single-stranded.
15. The method of claim 12 , wherein the oligonucleotide comprises at least one RNA nucleoside.