TPR is required for circRNA, lncRNA and mRNA nuclear export

Efficient RNA nuclear export is essential for proper cellular function and normal physiology, with defects in this process leading to pathological consequences. Our study aimed to investigate the role of translocated promoter region (TPR), nuclear basket protein, in orchestrating RNA transport in human cells as well as the function of TPR-mediated RNA nuclear export in cervical cancer cells.

RNA sequencing and bioinformatic analysis were applied to explore the effect of TPR on circular RNAs (circRNAs), long non-coding RNAs (lncRNAs), and mRNAs nuclear export and their corresponding sequence characteristic. Fluorescence in situ hybridization was employed to explore the role of TPR in RNA nuclear export. Immunofluorescence staining was used to study the role of TPR in R-loop and DNA damage. Flow cytometry assay was applied to investigate the influence of TPR on cell cycle in cervical cancer cells.

TPR depletion leads to the nuclear accumulation of 7243 circRNAs, 1913 lncRNAs, and 2758 mRNAs. Codepletion and rescue experiments suggested that the modulation of TPR-mediated circRNAs nuclear export might be independent of XPO4. The regulation of TPR-mediated circRNAs nuclear export is independent of circRNAs characteristics, while, the regulation of TPR-mediated lncRNAs and mRNAs nuclear export is partly dependent on lncRNAs/mRNAs transcription length. Moreover, the lack of TPR results in nuclear R-loop accumulation, causing DNA damage and cell cycle arrest as well as subsequent inhibition of cell proliferation in cervical cancer cells.

This study highlights the nuclear export of circRNA, lncRNA and mRNA relies critically on TPR, a mechanism that may inhibit nuclear accumulation of R-loop and DNA damage in cervical cancer cells.