Cancer initiating cells (CIC) undergo asymmetric growth patterns that increase phenotypic diversity and drive selection for chemotherapeutic resistance and tumor relapse. WNT signaling is a hallmark of colon CIC, often caused by APC mutations which enable activation of ß-catenin and MYC. Accumulating evidence indicates that long non-coding RNAs (lncRNA) contribute to the stem-like character of colon cancer cells. In this study, we report enrichment of the lncRNA RBM5-AS1/LUST during sphere formation of colon CIC. Its silencing impaired WNT signaling, whereas its overexpression enforced WNT signaling, cell growth and survival in serum-free media. RBM5-AS1 has been little characterized previously and we determined it to be a nuclear-retained transcript that selectively interacted with beta-catenin. Mechanistic investigations showed that silenccing or overexpression of RBM5-AS1 caused a respective loss or retention of beta-catenin from TCF4 complexes bound to the WNT target genes SGK1, YAP1 and MYC. Our work suggests that RBM5-AS1 activity is critical for the functional enablement of CIC cancer stem-like cells. Further, it defines the mechanism of action of RMB5-AS1 in the WNT pathway via physical interactions with beta-catenin, helping organize transcriptional complexes that sustain colon CIC function.