Abstract
Ribosomopathies are a group of rare diseases in which genetic mutations cause defects in either ribosome biogenesis or function, given specific phenotypes. Ribosomal proteins, and multiple other factors that are necessary for ribosome biogenesis (rRNA processing, assembly of subunits, export to cytoplasm), can be affected in ribosomopathies. Despite the need for ribosomes in all cell types, these diseases result mainly in tissue-specific impairments. Depending on the type of ribosomopathy and its pathogenicity, there are many potential therapeutic targets. The present manuscript will review our knowledge of ribosomopathies, discuss current treatments, and introduce the new therapeutic perspectives based on recent research. Diamond–Blackfan anemia, currently treated with blood transfusion prior to steroids, could be managed with a range of new compounds, acting mainly on anemia, such as L-leucine. Treacher Collins syndrome could be managed by various treatments, but it has recently been shown that proteasomal inhibition by MG132 or Bortezomib may improve cranial skeleton malformations. Developmental defects resulting from ribosomopathies could be also treated pharmacologically after birth. It might thus be possible to treat certain ribosomopathies without using multiple treatments such as surgery and transplants. Ribosomopathies remain an open field in the search for new therapeutic approaches based on our recent understanding of the role of ribosomes and progress in gene therapy for curing genetic disorders.
Highlights
Ribosomes, complexes composed of ~80 proteins and four rRNAs, forming two distinct subunits, are key actors in the development of cells’ proteome [1]
Pre-40S ribosomal subunit assembly and 18S rRNA processing are affected in Bowen–Conradi syndrome (BCS), North American Indian childhood cirrhosis (NAIC), isolated congenital asplenia (ICA), and 5q-syndrome (5q)
No pattern can be defined concerning the ribosome biogenesis stage affected and the tissues impacted in ribosomopathies
Summary
Complexes composed of ~80 proteins and four rRNAs, forming two distinct subunits, are key actors in the development of cells’ proteome [1]. Two pre-RNAs, 47S and 5S, are transcribed and processed sequentially by several ribosomal and non-ribosomal proteins in the nucleolus to produce the pre-40S and 60S subunits These pre-subunits are exported to the nucleoplasm, to the cytoplasm, through separate maturation pathways involving multiple factors. DBA, characterized by mutations in either RPLs or RPSs, impacts both pre-40S and 60S subunit biogenesis Maturation of both pre-subunits continues through separate pathways first in the nucleolus, in the nucleus to produce mature 40S and 60S subunits in the cytoplasm; (D) the 40S subunit, associated with several eIFs, scans mRNAs until encountering start codon AUG complementary to the Met-tRNA present in its P site. The aim of this manuscript is to review the current and new therapeutic perspectives of certain ribosomopathies
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
