RNA polymerase I subunit RPA43 activates rRNA expression and cell proliferation but inhibits cell migration

• Published in: Biochimica et biophysica acta. General subjects Vol. 1867; no. 9; p. 130411
• Main Authors: Zhang, Yue, Pang, Yaoyu, Zhang, Kewei, Song, Xiaoye, Gao, Junwei, Zhang, Shuting, Deng, Wensheng
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.09.2023
• Subjects: Cell migration; Cell proliferation; Ribosomal RNA expression; RNA polymerase I-directed transcription; RPA43; Cell proliferation; Ribosomal RNA expression; RPA43; RNA polymerase I-directed transcription; Cell migration
• ISSN: 0304-4165; 1872-8006
• DOI: 10.1016/j.bbagen.2023.130411

The products synthesized by RNA polymerase I (Pol I) play fundamental roles in several cellular processes, including ribosomal biogenesis, protein synthesis, cell metabolism, and growth. Deregulation of Pol I products can cause various diseases such as ribosomopathies, leukaemia, and solid tumours. However, the detailed mechanism of Pol I-directed transcription remains elusive, and the roles of Pol I subunits in rRNA synthesis and cellular activities still need clarification. In this study, we found that RPA43 expression levels positively correlate with Pol I product accumulation and cell proliferation, indicating that RPA43 activates these processes. Unexpectedly, RPA43 depletion promoted HeLa cell migration, suggesting that RPA43 functions as a negative regulator in cell migration. Mechanistically, RPA43 positively modulates the recruitment of Pol I transcription machinery factors to the rDNA promoter by activating the transcription of the genes encoding Pol I transcription machinery factors. RPA43 inhibits cell migration by dampening the expression of c-JUN and Integrin. Collectively, we found that RPA43 plays opposite roles in cell proliferation and migration except for driving Pol I-dependent transcription. These findings provide novel insights into the regulatory mechanism of Pol I-mediated transcription and cell proliferation and a potential pathway to developing anti-cancer drugs using RPA43 as a target. •RPA43 positively regulates Pol I-directed transcription.•RPA43 promotes cancer cell proliferation.•RPA43 inhibits cancer cell migration.•RPA43 activates the expression of Pol I transcription machinery factors.•RPA43 inhibits the expression of c-JUN and Integrin.