STAT3 promotes RNA polymerase III-directed transcription by controlling the miR-106a-5p/TP73 axis

Abstract

Deregulation of Pol III products causes a range of diseases, including neural diseases and cancers. However, the pathways and factors that control Pol III-directed transcription have yet to be elucidated. Here, we show that STAT3 positively regulates the activities of Pol III-dependent transcription and cancer cell growth. RNA-seq analysis revealed that STAT3 inhibits the expression of TP73, a member of the p53 family. We found that TP73 is not only required for the regulation of Pol III-directed transcription mediated by STAT3 but also independently suppresses the synthesis of Pol III products. Mechanistically, TP73 can disrupt the assembly of TFIIIB subunits and inhibit their occupancies at Pol III target loci by interacting with TFIIB subunit TBP. MiR-106a-5p can activate Pol III-directed transcription by targeting the TP73 mRNA 3′ UTR to reduce TP 73 expression. We show that STAT3 activates the expression of miR-106a-5p by binding to the microRNA promoter, indicating that miR-106a-5p links STAT3 to TP73 and Pol III transcription. Collectively, these findings indicate that STAT3 functions as a positive regulator in Pol III-directed transcription by controlling the miR-106a-5p/TP73 axis.