Fig. 3
From: Ribosomal proteins and human diseases: molecular mechanisms and targeted therapy
Altered mRNA translation in cells with ribosome biogenesis defects. a In normal cells, functional mature ribosomes (80S) comprise the small (40S) subunit and the large (60S) subunit. The small subunit interacts with the anticodon-containing ends of complementary tRNAs so as to translate the codon information contained in mRNA into its corresponding sequence of amino acids. The large subunit contains peptidyl transferase activity and is responsible for linking the amino acids into a polypeptide chain. b In ribosomopathies such as DBA (Diamond–Blackfan anemia), mutations in RPS19 can cause a decrease in the number of functional ribosomes, which may lead to a competition for ribosomes among cellular mRNAs, leading to changes in the translation efficiency of subsets of mRNAs, including reduced translation of GATA1 mRNA. Reduced levels of GATA1, a key erythroid transcription factor impairs erythroid lineage commitment and results in specific defects in erythropoiesis in DBA. c Ribosome defects due to RP mutations and variation in RP composition may generate heterogeneous ribosomes with reduced translation fidelity, resulting in altered translation patterns. In DBA patients, deficiencies in RPL11 or RPS19 due to mutations can reduce the translation of IRES-containing mRNAs BAG1 and CSDE1, which encode erythroblast proliferation and differentiation factors. In X-linked-Dyskeratosis Congenita, defects in rRNA pseudouridylation can impair the binding of ribosomes to IRES elements, resulting in reduced translational fidelity and decreased translation of several IRES-containing mRNAs, including p27, XIAP, and Bcl-xL and enhanced bone marrow failure and cancer susceptibility
