MAX-Mediated Transcriptional Regulation of Pseudouridine(Ѱ) Modified RNAs and Interacting RNA-Binding Proteins: Implications in Cancer Regulatory Networks

Abstract

Background: Pseudouridine modified mRNAs interact with RBPs and regulate various cellular processes including cell growth, proliferation and death. Ѱ is found to be a potential biomarker for several types of cancers. Ѱ modulates binding of various RBPs linked to cancer. However, transcriptional regulatory mechanisms coordinating these processes are still poorly understood. Objectives: To investigate the transcriptional regulatory mechanisms connecting pseudouridine-modified mRNAs, RBPs, and cancer hallmarks, focusing on the role of MAX in oncogenesis. Methods: We obtained the details of pseudouridine-modified sites on mRNA from available literatures and details of RBPs binding to it from ENCODE database. We used iRegulon to identify transcription factors regulating these mRNAs and RBPs. We performed functional enrichment analysis and assessed their implication in cancer. Result: Our analysis identified MAX (MYC associated factor X) as a key oncogenic transcription factor involving regulation of both Ѱ modified mRNAs and RBPs. It regulates oncogenic splicing factors like SRSF1, cancer associated helicase like DDX3X, DDX55 and protooncogenes like EXOSC5. MAX also regulates critical metabolism regulators like NOLC1 and ATP5E which play essential role in cancer cell metabolism and energy homeostasis. MAX mediated regulation of tumor suppressor PCBP1 and protooncogene IGF2BP3 indicates its dual regulatory influence in oncogenesis. This MAX-centered transcription regulatory network shows pseudouridine mediated cancer regulation through regulation of RBPs and RNA metabolism. Conclusion: This study highlights how Ѱ mediated processes are linked to cancer hallmarks by modulating RBP binding. This underscores therapeutic potential of targeting MAX mediated regulatory mechanism in cancer.