rDNA Transcription in Developmental Diseases and Stem Cells

As the first and rate-limiting step in ribosome biogenesis, rDNA transcription undergoes significant dynamic changes during cell pluripotency alteration. Over the past decades, rDNA activity has demonstrated dynamic changes, but most people view it as passive compliance with cellular needs. The evidence for rDNA transcriptional activity determining stem cell pluripotency is growing as research advances, resulting in the arrest of embryonic development and impairment of stem cell lines stemness by rDNA transcription inhibition. The exact mechanism by which rDNA activation influences pluripotency remains unknown. The first objective of this opinion article is to describe rDNA changes in the pathological and physiological course of life, including developmental diseases, tumor genesis, and stem cell differentiation. After that, we propose three hypotheses regarding rDNA regulation of pluripotency: 1) Specialized ribosomes synthesized from rDNA variant, 2) Nucleolar stress induced by the drop of rDNA transcription, 3) Interchromosomal interactions between rDNA and other genes. The pluripotency regulatory center is expected to focus strongly on rDNA. A small molecule inhibitor of rDNA is used to treat tumors caused by abnormal pluripotency activation. By understanding how rDNA regulates pluripotency, we hope to treat developmental diseases and safely apply somatic cell reprogramming in clinical settings.