Abstract

Regulation of protein synthesis is a vital step in controlling gene expression, especially during development. Over the last 10 years, it has become clear that rather than being homogeneous machines responsible for mRNA translation, ribosomes are highly heterogeneous and can play an active part in translational regulation. These “specialized ribosomes” comprise of specific protein and/or rRNA components, which are required for the translation of particular mRNAs. However, while there is extensive evidence for ribosome heterogeneity, support for specialized functions is limited. Recent work in a variety of developmental model organisms has shed some light on the biological relevance of ribosome heterogeneity. Tissue‐specific expression of ribosomal components along with phenotypic analysis of ribosomal gene mutations indicate that ribosome heterogeneity and potentially specialization are common in key development processes like embryogenesis, spermatogenesis, oogenesis, body patterning, and neurogenesis. Several examples of ribosome specialization have now been proposed but strong links between ribosome heterogeneity, translation of specific mRNAs by defined mechanisms, and role of these translation events remain elusive. Furthermore, several studies have indicated that heterogeneous ribosome populations are a product of tissue‐specific expression rather than specialized function and that ribosomal protein phenotypes are the result of extra‐ribosomal function or overall reduced ribosome levels. Many important questions still need to be addressed in order to determine the functional importance of ribosome heterogeneity to development and disease, which is likely to vary across systems. It will be essential to dissect these issues to fully understand diseases caused by disruptions to ribosomal composition, such as ribosomopathies.This article is categorized under:Translation > Translation RegulationTranslation > Ribosome Structure/FunctionRNA in Disease and Development > RNA in Development

Highlights

  • The regulation of mRNA translation is essential to developmental processes and their control, from embryogenesis to neurogenesis, across a myriad of organisms

  • BCL-2 is expressed at lower levels in autism (Fatemi et al, 2001), we do not know how the Leu206Met and His213Gln mutations may affect BCL-2 internal ribosome entry site (IRES)-mediated translation, this could provide a potential explanation for how RPL10-specialized ribosomes are linked to autism

  • Since 2011 and the reemergence of the theory of specialized ribosomes there has been substantial evidence provided for ribosome heterogeneity

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Summary

Introduction

The regulation of mRNA translation is essential to developmental processes and their control, from embryogenesis to neurogenesis, across a myriad of organisms. There is limited mechanistic detail to explain how different ribosome populations differentially regulate mRNA translation in the same cells or at a specific developmental time point. The caveat with specific phenotypes from RP mutants is that they are not necessarily the result of a requirement for an RP in the translation of specific mRNAs, that is, ribosome specialization.

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