CELL BASED METHODS AND SYSTEMS FOR THE IDENTIFICATION OF RNA REGULATORY SEQUENCES AND COMPOUNDS THAT MODULATE THEIR FUNCTIONS

摘要

The present invention is directed to an in vivo method for screening for and/or identifying RNA regulatory sequences involved in translational control. The method includes: culturing cells including: (i) a translational system; (ii) a reporter mRNA; and (iii) an RNA test sequence under suitable conditions for translation of the reporter mRNA, wherein the RNA test sequence is not attached to the reporter mRNA. The method also includes measuring the effect of the test sequence on the translation of the reporter mRNA, wherein a test sequence that modifies the translation of the reporter mRNA includes an RNA regulatory element. The invention also provides methods and systems for screening for and/or identifying test compounds that modulate the regulatory activity of an RNA regulatory sequence. This method includes culturing cells including (i) a translation system; (ii) a reporter mRNA; and (iii) an RNA regulatory sequence in the presence of at least one test compound, wherein the RNA regulatory sequence is not attached to the reporter mRNA. The ability of the test compound to affect the interaction between the RNA regulatory sequence and at least one component of the translation system is sought to be determined. The method further includes monitoring for the effect of the test compound on the this interaction, wherein a compound that modifies this interaction is a drug candidate.