Abstract
Most yeast ribosomal protein genes are duplicated and their characterization has led to hypotheses regarding the existence of specialized ribosomes with different subunit composition or specifically-tailored functions. In yeast, ribosomal protein genes are generally duplicated and evidence has emerged that paralogs might have specific roles. Unlike yeast, most mammalian ribosomal proteins are thought to be encoded by a single gene copy, raising the possibility that heterogenous populations of ribosomes are unique to yeast. Here, we examine the roles of the mammalian Rpl22, finding that Rpl22−/− mice have only subtle phenotypes with no significant translation defects. We find that in the Rpl22−/− mouse there is a compensatory increase in Rpl22-like1 (Rpl22l1) expression and incorporation into ribosomes. Consistent with the hypothesis that either ribosomal protein can support translation, knockdown of Rpl22l1 impairs growth of cells lacking Rpl22. Mechanistically, Rpl22 regulates Rpl22l1 directly by binding to an internal hairpin structure and repressing its expression. We propose that ribosome specificity may exist in mammals, providing evidence that one ribosomal protein can influence composition of the ribosome by regulating its own paralog.
Highlights
Protein synthesis is a major energy consuming process involving intricate coordination of translation machinery in response to nutrient availability and stress sensing signals, as well as hormonal and growth factor cues in multi-cellular organisms
We provide evidence that ribosomal proteins can influence the composition of the ribosome, which we hypothesize, may impact the function of the ribosome
A gene-trapped mouse embryonic stem cell clone harboring a mutation in Rpl22 was obtained from Bay Genomics and used to generate Rpl22 heterozygous mice (Rpl22+/2). 5’ rapid amplification of cDNA ends (59 RACE) followed by automated DNA sequencing determined that the gene-trap vector inserted between the third and fourth exons of Rpl22 (Figure S1A)
Summary
Protein synthesis is a major energy consuming process involving intricate coordination of translation machinery in response to nutrient availability and stress sensing signals, as well as hormonal and growth factor cues in multi-cellular organisms. The ribosome is comprised of two ribonucleoprotein subunits: the 40S and 60S (‘small’ and ‘large’ subunits, respectively). Together these subunits facilitate peptide bond formation, performing different roles during translation. A growing number of human diseases have been linked to mutations in genes encoding factors involved in ribosome biogenesis and protein synthesis [5,6]. These include developmental malformations, inherited bone marrow failure syndromes and cancer in a variety of organisms [5,7,8,9].
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