Non-coding RNAs (ncRNAs) are finely tuned cellular regulators important for human cell growth and cancer progression. DUBR (Dppa2 upstream binding RNA, also known as linc00883) is a nuclear ncRNA first discovered in mice for its role in regulating myoblast differentiation through interactions with chromatin and DNA methyltransferases. High expression levels of this ncRNA are predictive of poor patient outcome in colon adenocarcinoma, suggesting that DUBR may be involved in controlling cancer growth. To elucidate its function, we used RAP-MS and RNA immunoprecipitation techniques which revealed its interaction with epigenetic maintenance proteins in the human colon cancer cell line HCT116. Further, ATAC-seq and RNA-seq were used to address its function in regulating the epigenome and transcriptome of HCT116 cells. Here we report that DUBR is a regulator of human colon cancer cell line HCT116 survival. Additionally, we find that the ncRNA DUBR regulates AP-1 transcription factor binding site accessibility at enhancers of genes involved in differentiation and morphogenesis through interactions with epigenetic proteins such as NuRD complex members HDAC1 and CHD4.

TAR DNA-binding protein (TDP-43) and metastasis-associated lung adenocarcinoma transcript (MALAT1) RNA are both abundantly expressed in the human cell nucleus. Increased interaction of TDP-43 and MALAT1, as well as dysregulation of TDP-43 function, was previously identified in brain samples from patients with neurodegenerative disease compared to healthy brain tissues. We hypothesized that TDP-43 function may depend in part on MALAT1 expression levels. Here, we find that alterations in MALAT1 expression affect cell viability and can modulate TDP-43 binding to other mRNAs in HEK293 and SH-SY5Y human cell lines. Disruption of either MALAT1 or TDP-43 expression induces cell death, indicating that both macromolecules contribute positively to survival. Depletion of MALAT1 RNA results in increased binding of TDP-43 to other mRNA transcripts at the 3 UTR. Finally, we examined the contribution of MALAT1 expression to survival in a cell culture model of neurodegeneration using MPP+ treatment in SH-SY5Y cells. Depletion of MALAT1 RNA protects against toxicity in a cellular model of neurodegeneration and modulates TDP-43 binding to mRNA transcripts involved in apoptotic cell death. Taken together, we find that MALAT1 RNA and TDP-43 interactions can affect mRNA levels and cell viability. A tightly regulated network of noncoding RNA, messenger RNA, and protein interactions could provide a mechanism to maintain appropriate RNA expression levels and contribute to neuronal function.