The ribosomopathies comprise a group of disorders characterized by aberrant ribosome biogenesis and function, resulting in specific disease phenotypes.1 The 5q- syndrome, the most distinct of all the myelodysplastic syndromes (MDS),2 is now recognized as a ribosomopathy. The CD34+ cells of patients with the 5q- syndrome show haploinsufficiency of the ribosomal protein gene RPS14,3, 4 which maps to the commonly deleted region (CDR) on chromosome 5q. It has been demonstrated that p53 activation secondary to RPS14 haploinsufficiency has an important role in the development of anemia in the 5q- syndrome. Haploinsufficiency of RPS14 in the 5q- syndrome is associated with a block in the processing of pre-ribosomal RNA4 and deregulation of ribosomal- and translation-related genes. Defective ribosome biogenesis can result in a reduction in the efficiency of mRNA translation4, 8 and cultured erythroblasts from patients with the 5q- syndrome,8 and the ribosomopathy Schwachman-Diamond syndrome,9 exhibit impaired mRNA translation.

Activation of the mTOR signaling pathway by L-leucine in 5q-syndrome and other RPS14-deficient erythroblasts.

MECUCCI, Cristina;
2013

Abstract

The ribosomopathies comprise a group of disorders characterized by aberrant ribosome biogenesis and function, resulting in specific disease phenotypes.1 The 5q- syndrome, the most distinct of all the myelodysplastic syndromes (MDS),2 is now recognized as a ribosomopathy. The CD34+ cells of patients with the 5q- syndrome show haploinsufficiency of the ribosomal protein gene RPS14,3, 4 which maps to the commonly deleted region (CDR) on chromosome 5q. It has been demonstrated that p53 activation secondary to RPS14 haploinsufficiency has an important role in the development of anemia in the 5q- syndrome. Haploinsufficiency of RPS14 in the 5q- syndrome is associated with a block in the processing of pre-ribosomal RNA4 and deregulation of ribosomal- and translation-related genes. Defective ribosome biogenesis can result in a reduction in the efficiency of mRNA translation4, 8 and cultured erythroblasts from patients with the 5q- syndrome,8 and the ribosomopathy Schwachman-Diamond syndrome,9 exhibit impaired mRNA translation.
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11391/1370868
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