Compositions and Methods for Regulating RNA Translation via CD154 CA-Dinucleotide Repeat

Abstract

Compositions and methods for regulating CD154 gene expression are provided that rely on the interaction of hnRNP L with the CA-dinucleotide rich sequence of the 3′-untranslated region of CD154.

1 . A method for inhibiting the nuclear export or translation of a ribonucleic acid comprising contacting a cell or tissue containing a CA-dinucleotide rich sequence of the CD154 mRNA 3′-untranslated region operatively-linked to a ribonucleic acid with an agent which binds to the CA-dinucleotide rich sequence so that the nuclear export or translation of the ribonucleic acid is inhibited. 
     
     
         2 . A method for modulating the nuclear export or translation of a ribonucleic acid comprising contacting a cell or tissue containing a CA-dinucleotide rich sequence of the CD154 mRNA 3′-untranslated region operatively-linked to a ribonucleic acid with an agent which modulates the level or activity of an hnRNP L protein so that the nuclear export or translation of the ribonucleic acid is modulated. 
     
     
         3 . A method for preventing or treating a disease or condition associated with CD154-CD40 interactions comprising administering to a subject in need of treatment an agent which binds to a CA-dinucleotide rich sequence of the CD154 mRNA 3′-untranslated region so that CD154 translation is inhibited thereby preventing or treating the disease or condition associated with CD154-CD40 interactions. 
     
     
         4 . A method for preventing or treating a disease or condition associated with CD154-CD40 interactions comprising administering to a subject in need of treatment an agent which modulates the level or activity of hnRNP L protein so that the disease or condition associated with CD154-CD40 interactions is prevented or treated. 
     
     
         5 . A method for identifying agents that modulate the level or activity of hnRNP L comprising contacting a test cell containing hnRNP L protein, and a CA-dinucleotide rich sequence of the CD154 mRNA 3′-untranslated region operatively-linked to a nucleic acid encoding a reporter protein, with an agent and detecting reporter protein expression in the test cell, wherein
 a decrease in reporter protein expression in the test cell contacted with the agent relative to reporter protein expression in a test cell not contacted with the agent, indicates that the agent increases the level or activity of hnRNP L in the cell, and   an increase in reporter protein expression in the test cell contacted with the agent relative to reporter protein expression in a test cell not contacted with the agent, indicates that the agent decreases the level or activity of hnRNP L in the cell.   
     
     
         6 . An agent identified by the method of  claim 5 .