The noncoding RNA linc-ADAMTS5 cooperates with RREB1 to protect from intervertebral disc degeneration through inhibiting ADAMTS5 expression

In this study, through mining computational algorithm programs, and public available data sets, we identified Ras responsive element binding protein 1 (RREB1) as a crucial transcription factor regulating the expression of ADAMTS5 in NP cells. RNA pull-down, RNA immunoprecipitation, in vitro binding assays, and gain- and loss-of-function studies indicated that a physical interaction between linc-ADAMTS5 and splicing factor proline/glutamine-rich (SFPQ) facilitated the recruitment of RREB1 to binding sites within the ADAMTS5 promoter to induce chromatin remodeling. This resulted in subdued ADAMTS5 levels in cultured NP cells involving histone deacetylases. In clinical NP tissues, linc-ADAMTS5 and RREB1 were correlated negatively with ADAMTS5 expression. Taken together, these results demonstrate that RREB1 cooperates with noncoding RNA linc-ADAMTS5 to inhibit ADAMTS5 expression, thereby affecting degeneration of the extracellular matrix of the intervertebral disc.

Source: Clinical Science - March 24, 2017 Category: Biomedical Science Authors: Wang, K., Song, Y., Liu, W., Wu, X., Zhang, Y., Li, S., Kang, L., Tu, J., Zhao, k., Hua, W., Yang, C. Tags: PublishAheadOfPrint Source Type: research