Venue: Level 12 Conference Room
Time: 11am

Scientific work presentation:

Speaker: Shi Hao TAN (from Takaomi Sanda’s group)

Title: Identification of Long Non-Coding RNAs Regulated by the TAL1 Complex in T-cell Acute Lymphoblastic Leukemia

Abstract:

TAL1/SCL is one of the most prevalent oncogenes in T-cell acute lymphoblastic leukemia (T-ALL). TAL1 and its regulatory partners (GATA3, RUNX1, and MYB) positively regulate each other and coordinately regulate the expression of their downstream target genes in T-ALL cells. However, long non-coding RNAs (lncRNAs) regulated by these factors are largely unknown. Here we established a bioinformatics pipeline and analyzed RNA-seq datasets to identify lncRNAs regulated by TAL1 in T-ALL. Our analysis predicted 57 putative lncRNAs that are activated by TAL1, many of which were regulated by GATA3, RUNX1, and MYB in a coordinated manner. We identified two novel transcripts that were activated in multiple T-ALL cell samples but were downregulated in normal thymocytes. One novel lncRNA transcript near the ARID5B gene locus which we named ARIEL (ARID5B Inducing Enhancer-associated Long Non-Coding RNA) was specifically expressed in TAL1-positive T-ALL cases. ARID5B was recently identified as important for T-ALL leukemogenesis and we further explored the role of the neighbourhood lncRNA ARIEL. Further analysis our Chip-seq data showed that ARIEL is aberrantly expressed from the -135kb enhancer region of ARID5B in TAL1-positive cells. Knockdown of ARIEL resulted in a significant decrease of the levels of ARID5B at the mRNA and protein levels together with a loss of chromatin interaction between this enhancer and ARID5B promoter region as observed by 4C-seq. We also show through RNA Immunoprecipitation (RIP) that ARIEL is able to interact with Mediator 12. Overall, our study shows that the ARIEL can act as an enhancer RNA to regulate expression of the oncogenic ARID5B by mediating enhancer-promoter chromatin interaction in T-ALL leukemogenesis.