Functions of the ribosomal factors block of proliferation 1 and ribosomal protein L5 during embryogenesis of Xenopus laevis

Abstract

Ribosomes are the molecular machine that translates the genetic information from intermediate mRNA into proteins. Hence, ribosomal biogenesis is a crucial process which requires a tremendous amount of energy and hundreds of different factors. Defects in this process result in pathological condition termed ribosomopathy. The two ribosomal factors block of proliferation 1 (Bop1) and ribosomal protein L5 (Rpl5) were investigated in this study. Bop1 is required for the maturation of the 28S rRNA and 5.8S rRNA and has not been associated with ribosomopathies yet. However, Bop1 has been associated with several cancers. Rpl5 builds a ribonucleoprotein complex with 5S rRNA and as a complex it is incorporated into the large subunit of the ribosome. Mutations in the RPL5 gene have been associated with the ribosomopathy Diamond Blackfan anemia. Here, it is shown that the knockdown of Bop1 and Rpl5 in the anterior tissue of Xenopus laevis embryos resulted in severe phenotypes including smaller eyes, smaller brain, and malformed cranial cartilage. In addition, the expression of tissue specific marker genes was affected upon Bop1 and Rpl5 depletion. A common signaling pathway of Bop1 and Pax6 is suggested upon synergy experiments. In contrast to Bop1, Rpl5 depletion resulted in reduced proliferation and increased apoptosis. A common signaling pathway was found between Rpl5 and Tp53. The co-injection of the apoptosis blocker bcl2 partially rescued the phenotype which resulted of Rpl5 knockdown. This indicates that apoptosis majorly contributes to the Rpl5 knockdown-induced phenotype.