A possible association between Zika virus infection and CDK5RAP2 mutations

摘要

Tie2 mediates an inhibitory signal for vessel growth in order to fine-tune vessel architecture during embryonic development. Ribosome, composed of ribosomal RNA (rRNA) and proteins (RPs), is the molecular machine that translates mRNAs into pro- teins. A conventional view on ribosomes is that they are composed of a non-varying composition of rRNA and RPs and that they play a passive role in mRNA translation. Accumulating evidence, how- ever, suggests that ribosome heterogeneity exits, at least, at the organismal level and that different RPs in the ribosome may con- fer it mRNA binding and translational selectivity. This notion is supported by several pieces of evidence that hypomorphic muta- tions in RP genes lead to tissue-specific defects, suggesting that the translation of a specific set of mRNAs may be affected when a specific RP is missing. Bellyspot and tail (Bst), is one such muta- tion in mouse, which is a hypomorphic mutation in rpl24 gene and whose phenotype includes selective loss of retinal ganglion cells (RGCs) and their axons, the optic nerve. In this study, we investigate whether ribosome heterogeneity contributes to the manifestation of the tissue-specific defects in Bst mouse. Specifically, we perform polysome profiling in tissues affected and not affected by this muta- tion and ask whether a decrease or increase in the translation of specific sets of mRNAs can account for the loss of RGCs. The results of this study may shed new insights into a deeper understanding of ribosomopathies in human.