Nucleic acid sequences and methods for identifying compounds that affect RNA/RNA binding protein interactions and mRNA functionality
Disclosed herein are nucleic acid sequences and their optimized subfragments which are located in the mRNA untranslated regions of therapeutically-relevant genes. These sequences specifically bind RNA binding proteins (RBPs) and/or regulate the mRNA functionality. Also disclosed are methods of optimizing a subfragment of a parent nucleic acid sequence such that the RBP binding activity or mRNA functionality of the parent nucleic acid sequence is preserved in the optimized subfragment.
1 . An isolated fusion nucleic acid, comprising a first nucleic acid operably linked to a heterologous second nucleic acid, wherein said first nucleic acid comprises SEQ ID NO: 17, and wherein the mRNA form of said first nucleic acid has RNA binding protein (RBP) binding activity or regulates the functionality of the mRNA form of said fusion nucleic acid.
2 . The isolated fusion nucleic acid of claim 1 , wherein said fusion nucleic acid is DNA.
3 . The isolated fusion nucleic acid of claim 2 , wherein said DNA is cDNA.
4 . The isolated fusion nucleic acid of claim 1 , wherein said fusion nucleic acid is mRNA.
5 . The isolated fusion nucleic acid of claim 1 , wherein said first nucleic acid has RNA binding protein (RBP) binding activity.
6 . The isolated fusion nucleic acid of claim 1 , wherein said first nucleic acid regulates the functionality of the mRNA form of said fusion nucleic acid.
7 . The isolated fusion nucleic acid sequence of claim 6 , wherein the regulation of mRNA functionality comprises an alteration in pre-mRNA processing or in the stabilization, translational efficiency, localization, sequestration, editing, or splicing function of said mRNA form of said fusion nucleic acid.