Long noncoding RNAs (lncRNAs) act by a host of mechanisms to impact genomic expression. To identify lncRNAs with essential roles in differentiation, we undertook a systematic screen to identify Terminal differentiation Induced NonCoding RNA (TINCR). TINCR controlled expression of hundreds of genes by a novel post-transcriptional mechanism that involved complementary base pairing by TINCR to target mRNAs through a 25nt “TINCR” box sequence. TINCR stabilized bound differentiation gene mRNAs in concert with the Staufen 1 protein, demonstrating an entirely new mechanism for lncRNA action