TY - JOUR
T1 - Molecular etiology of defective nuclear and mitochondrial ribosome biogenesis
T2 - Clinical phenotypes and therapy
AU - Jerome, Maria Sona
AU - Nanjappa, Dechamma Pandyanda
AU - Chakraborty, Anirban
AU - Chakrabarty, Sanjiban
N1 - Funding Information:
This work was supported by Science and Engineering Research Board (SERB) , Department of Science and Technology , Government of India ( YSS/2015/001051 and CRG/2020/004681 ).
Funding Information:
The authors gratefully acknowledge infrastructure funding from DST-FIST, Government of India , K-FIST, Government of Karnataka , TIFAC-CORE , VGST Karnataka, DBT-Builder grant , Manipal School of Life Sciences, and Manipal Academy of Higher Education .
Publisher Copyright:
© 2022 Elsevier B.V. and Société Française de Biochimie et Biologie Moléculaire (SFBBM)
PY - 2023/4
Y1 - 2023/4
N2 - Ribosomopathies are rare congenital disorders associated with defective ribosome biogenesis due to pathogenic variations in genes that encode proteins related to ribosome function and biogenesis. Defects in ribosome biogenesis result in a nucleolar stress response involving the TP53 tumor suppressor protein and impaired protein synthesis leading to a deregulated translational output. Despite the accepted notion that ribosomes are omnipresent and essential for all cells, most ribosomopathies show tissue-specific phenotypes affecting blood cells, hair, spleen, or skin. On the other hand, defects in mitochondrial ribosome biogenesis are associated with a range of clinical manifestations affecting more than one organ. Intriguingly, the deregulated ribosomal function is also a feature in several human malignancies with a selective upregulation or downregulation of specific ribosome components. Here, we highlight the clinical conditions associated with defective ribosome biogenesis in the nucleus and mitochondria with a description of the affected genes and the implicated pathways, along with a note on the treatment strategies currently available for these disorders.
AB - Ribosomopathies are rare congenital disorders associated with defective ribosome biogenesis due to pathogenic variations in genes that encode proteins related to ribosome function and biogenesis. Defects in ribosome biogenesis result in a nucleolar stress response involving the TP53 tumor suppressor protein and impaired protein synthesis leading to a deregulated translational output. Despite the accepted notion that ribosomes are omnipresent and essential for all cells, most ribosomopathies show tissue-specific phenotypes affecting blood cells, hair, spleen, or skin. On the other hand, defects in mitochondrial ribosome biogenesis are associated with a range of clinical manifestations affecting more than one organ. Intriguingly, the deregulated ribosomal function is also a feature in several human malignancies with a selective upregulation or downregulation of specific ribosome components. Here, we highlight the clinical conditions associated with defective ribosome biogenesis in the nucleus and mitochondria with a description of the affected genes and the implicated pathways, along with a note on the treatment strategies currently available for these disorders.
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U2 - 10.1016/j.biochi.2022.11.001
DO - 10.1016/j.biochi.2022.11.001
M3 - Review article
C2 - 36336106
AN - SCOPUS:85141797588
SN - 0300-9084
VL - 207
SP - 122
EP - 136
JO - Biochimie
JF - Biochimie
ER -