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

Deregulation of Pol III products causes a range of diseases, including neural diseases and cancers. However, the factors and mechanisms that modulate Pol III-directed transcription remain to be found, although massive advances have been achieved. 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 TFIIIB 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 miRNA promoter, indicating that the miR-106a-5p links STAT3 with TP73 to regulate Pol III-directed 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.

Automated summary

Deregulation of Pol III products leads to various diseases, including neural diseases and cancers. STAT3 positively regulates Pol III-mediated transcription and cancer cell growth. TP73 plays a crucial role in both STAT3-modulated Pol III transcription and independent suppression of Pol III product synthesis. MiR-106a-5p activates Pol III transcription by targeting TP73 mRNA, and STAT3 activates miR-106a-5p expression, connecting STAT3 with TP73 to regulate Pol III transcription.