Date Published: November 3, 2016
Publisher: Public Library of Science
Author(s): Anupama Yadav, Aparna Radhakrishnan, Anshuman Panda, Amartya Singh, Himanshu Sinha, Gyan Bhanot, Michael Polymenis.
The ribosome is an ancient machine, performing the same function across organisms. Although functionally unitary, recent experiments suggest specialized roles for some ribosomal proteins. Our central thesis is that ribosomal proteins function in a modular fashion to decode genetic information in a context dependent manner. We show through large data analyses that although many ribosomal proteins are essential with consistent effect on growth in different conditions in yeast and similar expression across cell and tissue types in mice and humans, some ribosomal proteins are used in an environment specific manner. The latter set of variable ribosomal proteins further function in a coordinated manner forming modules, which are adapted to different environmental cues in different organisms. We show that these environment specific modules of ribosomal proteins in yeast have differential genetic interactions with other pathways and their 5’UTRs show differential signatures of selection in yeast strains, presumably to facilitate adaptation. Similarly, we show that in higher metazoans such as mice and humans, different modules of ribosomal proteins are expressed in different cell types and tissues. A clear example is nervous tissue that uses a ribosomal protein module distinct from the rest of the tissues in both mice and humans. Our results suggest a novel stratification of ribosomal proteins that could have played a role in adaptation, presumably to optimize translation for adaptation to diverse ecological niches and tissue microenvironments.
A single celled organism displays a range of phenotypes to survive in diverse environments. In complex multicellular organisms, in addition to the external environment, tissue specific cell types display specialized mechanisms to regulate phenotype in local tissue environments. Much of the research in biology has been directed towards understanding the basis of the information flow that gives rise to these diverse phenotypes. This has resulted in the identification of many regulatory processes [1,2] which fine-tune transcriptional expression and modulate the translation of mRNA into proteins [3,4] in response to external and environmental or tissue specific signaling cues. However, in spite of its essential role in this cellular information flow, the ribosome has always been regarded as an inert participant in the information flow that regulates cellular and tissue states.
Our study provides several arguments and multiple evidences for the existence of modularity of ribosomal proteins across eukaryota, presumably to facilitate optimized translation efficiency in different environments. We show that, at least in yeast, we see evidence that the 5’UTRs of ribosomal proteins that form the modules seem to be under selection pressure, which suggests that they play a role in evolutionary adaptation. We interpret our results as evidence for a hitherto unrecognized ribosomal code, wherein specific ribosomal proteins are used in an environment specific manner in yeast and in cell and tissue specific ways in mice and humans. The existence of such a dynamic modularity of ribosomal proteins is the main finding of this paper. The mechanisms that regulate these modules remain to be elucidated and are outside the scope of this paper.