研究动态
Articles below are published ahead of final publication in an issue. Please cite articles in the following format: authors, (year), title, journal, DOI.

rDNA转录在发育性疾病和干细胞中。

rDNA Transcription in Developmental Diseases and Stem Cells.

发表日期:2023 Jan 12
作者: Yuchen Sun, Xinglin Hu, Dan Qiu, Zhijing Zhang, Lei Lei
来源: Stem Cell Reviews and Reports

摘要:

作为核糖体生物合成的第一步和速率限制步骤,rDNA转录在细胞多能性改变过程中经历了显著的动态变化。在过去的几十年中,rDNA活动已经表现出动态变化,但大多数人认为它是对细胞需求的被动响应。随着研究的进展,证据表明 rDNA转录活性决定干细胞多能性,而通过抑制 rDNA转录来诱导胚胎发育停滞和损伤干细胞系的干性。rDNA激活影响多能性的确切机制仍然未知。本文意见的第一个目标是描述人生病理和生理过程中rDNA的变化,包括发育疾病、肿瘤发生和干细胞分化。接下来,我们提出了三种关于rDNA调控多能性的假设:1)专门由rDNA变异合成的核糖体,2)rDNA转录下降引起的核仁应激,3)rDNA和其他基因之间的染色体间相互作用。 pluripotency调节中心预计将强烈关注rDNA。小分子抑制剂可用于治疗由异常多能性激活引起的肿瘤。通过了解rDNA如何调节多能性,我们希望治疗发育性疾病并在临床环境中安全应用体细胞重编程。©2023年。作者(s),在Springer Science + Business Media,LLC的独家许可下,包括Springer Nature。
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.© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.