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Ribosomes take control

The ribosome plays a universally conserved role in catalyzing the translation of all mRNAs in every cell across all kingdoms of life. It is therefore not surprising that the ribosome is considered one of the most complex and elaborately formed “molecular machines” in the cell, whose biogenesis is extraordinarily orchestrated, requiring all three RNA polymerases and more than 150 nonribosomal factors (1). Indeed, ribosomes make up much of the cell’s mass, and the eukaryotic ribosome is comprised of four RNA species and 79 ribosomal proteins (RPs). For decades, the dogma has been that, although the ribosome plays a critical function in translating the genomic code, it is largely a “back-stage” participant in gene regulation. This view has been reinforced by the widespread belief, early in the advent of the molecular era, that transcription rather than translation is the major molecular rheostat of gene expression. On the contrary, recent emerging evidence now reveals tremendous variation between expression of the transcriptome and proteome and that the cellular abundance of proteins may be predominantly controlled at the level of translational control (2). By extension, an interesting emerging question is whether the ribosome exerts a previously unappreciated regulatory function or specificity in translational control (3). A PNAS study by Lee et al. contributes to the growing realization of a surprising and emerging role for the ribosome as a “front-stage” participant in gene regulation (4). Moreover, their studies strongly suggest that much can be learned with respect to specialized mechanisms for cellular mRNA translation through the study of viral gene expression.