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rDNA Transcription in Developmental Diseases and Stem Cells

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Abstract

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.

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Abbreviations

5’UTR :

5’Untranslated regions

Act D :

Actinomycin D

ATRA :

All-trans-retinoic acid

AD :

Alzheimer's disease

ALS :

Amyotrophic lateral sclerosis

ASD :

Autism spectrum disorder

CIN :

Cervical intraepithelial neoplasia

3C :

Chromosome Conformation Capture

4C :

Chromosome conformation capture on chip

DFC :

Dense fibrillar center

EGA :

Embryonic gene activation

ESC :

Embryonic stem cells

EGF :

Epidermal growth factor

FC :

Fibrillar center

FMRP :

Fragile-X mental retardation protein

FTD :

Frontotemporal dementia

GO :

Gene Ontology

GSC :

Germline stem cells

GC :

Granular component

HSC :

Hematopoietic stem cells

HGSOC :

High grade serous ovarian cancer

Hi-C :

High-throughput chromatin conformation capture technology

HDACi :

Histone deacetylase inhibitor

HCC :

Human hepatocellular carcinoma

h-iPSCs :

Human induce pluripotent stem cells

HD :

Huntington's disease

iPSCs :

Induced pluripotent stem cells

IR :

Ionizing irradiation

mTOR :

Mammalian target of rapamycin

MET :

Mesenchymal-to-epithelial transition

NBS1 :

Nijmegen breakage syndrome protein 1

NORs :

Nucleolar organizer regions

OSCC :

Oral squamous cell carcinoma

PD :

Parkinson's disease

PMA :

Phorbol 12-myristate 13-acetate

PRC2 :

Polycomb repressive complex 2

pre-rRNA :

Precursor rRNA

SL-1 :

Promoter-selectivity factor

RHS7 :

rad50 hypersensitive site 7

RPS :

Ribosomal proteins

Ribo-seq :

Ribosome profiling sequencing

pol I :

RNA polymerase I complex

SCNT :

Somatic cell nuclear transfer

SIM :

Structural illumination superresolution microscopy

T-ALL :

T-cell acute lymphoblastic leukemia

TCS :

Treacher Collins Syndrome

TGC :

Trophoblast giant cells

TIP5 :

TTF-I-interacting protein 5

Tau :

Tubulin associated units

WGS :

Whole-genome sequencing

ZGA :

Zygotic genome activation

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Acknowledgements

We thank all the members in L.L.’s laboratory. This work was financially supported by the Key projects of Heilongjiang Natural Science Foundation (NO. ZD2021C005).

Funding

This work was supported by the Key projects of Heilongjiang Natural Science Foundation (NO. ZD2021C005).

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YC Sun: Article writer who drafted and mainly revised the work;

XL Hu: Participate in discussion and revision of articles;

D Qiu: Participate in revision and performed the literature search;

ZJ Zhang: Participate in discussion;

L Lei: Participate in article theme design, discussion and revision.

All authors read and approved the final manuscript.

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Correspondence to Lei Lei.

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Sun, Y., Hu, X., Qiu, D. et al. rDNA Transcription in Developmental Diseases and Stem Cells. Stem Cell Rev and Rep 19, 839–852 (2023). https://doi.org/10.1007/s12015-023-10504-6

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