Pseudogenes and Liquid Phase Separation in Epigenetic Expression

Abstract

Pseudogenes have been considered as non-functional genes. However, peptides and long non-coding RNAs produced by pseudogenes are expressed in different tumors. Moreover, the dysregulation of pseudogenes is associated with cancer, and their expressions are higher in tumors compared to normal tissues. Recent studies show that pseudogenes can influence the liquid phase condensates formation. Liquid phase separation involves regulating different epigenetic stages, including transcription, chromatin organization, 3D DNA structure, splicing, and post-transcription modifications like m⁶A. Several membrane-less organelles, formed through the liquid phase separate, are also involved in the epigenetic regulation, and their defects are associated with cancer development. However, the association between pseudogenes and liquid phase separation remains unrevealed. The current study sought to investigate the relationship between pseudogenes and liquid phase separation in cancer development, as well as their therapeutic implications.

Keywords: RNA modification; cancer; epigenetic; liquid phase separation; pseudogenes.

Figure 1

Interaction between pseudogenes and LLPS to mediate cancer: Pseudogenes can be produced in three processes: pseudogenes due to nonsense mutation, pseudogene due to DNA duplication, and processed pseudogenes as the result of retrotransposition machinery. Both LINE-1 and pseudogenes can mediate the liquid phase condensates formation. A defect in pseudogenes expression may affect the liquid phase separate process, eventually affecting the epigenetic mediators, including chromatin organization, DNA 3D structure, transcription factors, alternative splicing, and m⁶A modification. Abnormal expression in these epigenetic mediators promotes cancer development.

Figure 2

Overview of involvement of pseudogene in different cancer in the human body. Icons of body parts for the refrence are taken from different websources.