Specialized ribosomes: a new frontier in gene regulation and organismal biology

Key Points Historically, the ribosome has been viewed as a constitutive molecular machine with little regulatory capacity in mRNA translation. However, recent findings suggest that ribosome composition and activity may be more dynamically regulated to impart a new layer of specificity in the control of gene expression. Studies in several species have shown that 'specialized ribosomes' may exist, and that these ribosomes display heterogeneity in the composition and post-translational modifications of subsets of ribosomal proteins, variations in ribosomal RNA (rRNA) sequences or binding to distinct ribosome-associated factors. Greater variations in the translation machinery may have an substantial impact on how the genomic template is translated into functional proteins. Specific cis -acting 'translational regulons' within mRNAs may interface with specialized ribosomes to confer translational specificity. Examples of these elements include internal ribosomal entry sites (IRESs) and upstream open reading frames (uORFs). Moreover, even core ribosome components that show little variation may exert a more specialized activity by virtue of their interactions with these specific regulatory elements. Regulation in ribosome activity may provide an important new layer for control of gene expression in time and space that has an effect on cell and organismal biology as well as human disease. It will be important to conceptualize mRNA translation in the same light as transcriptional control — as a process in which enhancers or attenuators are likely to fine-tune protein abundance and that culminates in unique readouts with important biological significance. Traditionally, ribosomes have been viewed as invariable complexes with ubiquitous function in mRNA translation. However, ribosome specialization, resulting from the differential expression and cell type-specific modification of its components, seems to greatly contribute to the diversity of biological processes. Historically, the ribosome has been viewed as a complex ribozyme with constitutive rather than intrinsic regulatory capacity in mRNA translation. However, emerging studies reveal that ribosome activity may be highly regulated. Heterogeneity in ribosome composition resulting from differential expression and post-translational modifications of ribosomal proteins, ribosomal RNA (rRNA) diversity and the activity of ribosome-associated factors may generate 'specialized ribosomes' that have a substantial impact on