Abstract
Ribosomes are essential components of the protein translation machinery and are composed of more than 80 unique large and small ribosomal proteins. Recent studies show that in addition to their roles in protein translation, ribosomal proteins are also involved in extra-ribosomal functions of DNA repair, apoptosis and cellular homeostasis. Consequently, alterations in the synthesis or functioning of ribosomal proteins can lead to various hematologic disorders. These include congenital anemias such as Diamond Blackfan anemia and Shwachman Diamond syndrome; both of which are associated with mutations in various ribosomal genes. Acquired uniallelic deletion of RPS14 gene has also been shown to lead to the 5q syndrome, a distinct subset of MDS associated with macrocytic anemia. Recent evidence shows that specific ribosomal proteins are overexpressed in liver, colon, prostate and other tumors. Ribosomal protein overexpression can promote tumorigenesis by interactions with the p53 tumor suppressor pathway and also by direct effects on various oncogenes. These data point to a broad role of ribosome protein alterations in hematologic and oncologic diseases.
Highlights
Eukaryotes have 80 S ribosomes, each consisting of a small (40 S) and large (60 S) subunit
Non hodgkins lymphoma: RPS6 is highly expressed in Diffuse large B cell lymphomas and genetic modulation of RPS6 protein levels with targeted short hairpin RNAs lead to a decrease in the actively proliferating population of cells compared with control shRNA
When the mice with the conditional deletion of a set of genes found in the common deleted region of the 5q- syndrome were crossed with p53 null mice, there was a complete rescue of the erythroid phenotype [19]. These findings indicate that p53 induction is critical for the macrocytic anemia caused by ribosomal dysfunction
Summary
Eukaryotes have 80 S ribosomes, each consisting of a small (40 S) and large (60 S) subunit. In E.coli, in addition to these functions, ribosomal proteins have been found to play a role in DNA replication, transcription and RNA processing [2,3] The involvement of these extraribosomal functions in the pathogenesis of ribosomopathies and cancer is reviewed in this article. 3. Treacher collins syndrome (TCS): called mandibulofacial dysostosis, TCS is a rare autosomal dominant congenital disorder characterized by craniofacial abnormalities such as micrognathia, malformed or absent external ears, underdeveloped zygoma, downward slanting eyes, conductive hearing loss, colobomata of the lower eye lids, cleft palate, brachycephaly, variable degree of facial nerve involvement [22]. Mice haploinsufficient for TCOF1 have diminished production of ribosomes and this has been shown to correlate with decreased production of neural crest precursor cells [25] This in turn leads to decreased number of neural crest cells migrating to the first and second pharyngeal arches, resulting in the development of the syndrome. The link between ribosomopathies and p53 activation will be discussed later in the review
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