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The ribosomal protein Rpl22 controls ribosome composition by directly repressing expression of its own paralog, Rpl22l1.

O'Leary MN, Schreiber KH, Zhang Y, Duc AC, Rao S, Hale JS, Academia EC, Shah SR, Morton JF, Holstein CA, Martin DB, Kaeberlein M, Ladiges WC, Fink PJ, Mackay VL, Wiest DL, Kennedy BK - PLoS Genet. (2013)

Bottom Line: 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.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.

View Article: PubMed Central - PubMed

Affiliation: Department of Biochemistry, University of Washington, Seattle, Washington, United States of America.

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.

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Mouse Rpl22 has an expressed paralog, Rpl22l1.(A) Alignment of Rpl22 and Rpl22l1 protein sequences. Lung, liver, spleen, kidney and pancreas, harvested from Rpl22−/− mice and their littermate controls, were analyzed for relative Rpl22 and Rpl22l1 mRNA levels by qRT-PCR (B) or protein expression by Western blot analysis (C). Results are representative of 3 independent experiments.
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pgen-1003708-g001: Mouse Rpl22 has an expressed paralog, Rpl22l1.(A) Alignment of Rpl22 and Rpl22l1 protein sequences. Lung, liver, spleen, kidney and pancreas, harvested from Rpl22−/− mice and their littermate controls, were analyzed for relative Rpl22 and Rpl22l1 mRNA levels by qRT-PCR (B) or protein expression by Western blot analysis (C). Results are representative of 3 independent experiments.

Mentions: We considered the possibility that another factor might be compensating for lack of Rpl22 in mice. A bioinformatic search identified Rpl22-like1 (Rpl22l1) as a candidate. Rpl22l1 encodes a 122 amino acid protein that is 73% identical to Rpl22 (Figure 1A). The protein sequence of Rpl22l1 is highly conserved from human to zebrafish (Figure S5). To determine if significant levels of Rpl22l1 mRNA exists in tissues from Rpl22+/+ mice and whether Rpl22l1 transcript levels increase in Rpl22−/− mice, lung, liver, spleen and kidney were harvested from Rpl22−/− mice and their littermate controls and analyzed by quantitative RT-PCR (qRT-PCR) for Rpl22 and Rpl22l1 expression with Acidic Ribosomal Protein (ARBP) mRNA levels used for normalization (Figure 1B). In Rpl22+/+ samples, high Rpl22 expression was detected, while Rpl22l1 transcripts were less abundant. In samples isolated from Rpl22−/− mice, qRT-PCR revealed a ∼3-fold induction of Rpl22l1 mRNA expression relative to littermate controls.


The ribosomal protein Rpl22 controls ribosome composition by directly repressing expression of its own paralog, Rpl22l1.

O'Leary MN, Schreiber KH, Zhang Y, Duc AC, Rao S, Hale JS, Academia EC, Shah SR, Morton JF, Holstein CA, Martin DB, Kaeberlein M, Ladiges WC, Fink PJ, Mackay VL, Wiest DL, Kennedy BK - PLoS Genet. (2013)

Mouse Rpl22 has an expressed paralog, Rpl22l1.(A) Alignment of Rpl22 and Rpl22l1 protein sequences. Lung, liver, spleen, kidney and pancreas, harvested from Rpl22−/− mice and their littermate controls, were analyzed for relative Rpl22 and Rpl22l1 mRNA levels by qRT-PCR (B) or protein expression by Western blot analysis (C). Results are representative of 3 independent experiments.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3750023&req=5

pgen-1003708-g001: Mouse Rpl22 has an expressed paralog, Rpl22l1.(A) Alignment of Rpl22 and Rpl22l1 protein sequences. Lung, liver, spleen, kidney and pancreas, harvested from Rpl22−/− mice and their littermate controls, were analyzed for relative Rpl22 and Rpl22l1 mRNA levels by qRT-PCR (B) or protein expression by Western blot analysis (C). Results are representative of 3 independent experiments.
Mentions: We considered the possibility that another factor might be compensating for lack of Rpl22 in mice. A bioinformatic search identified Rpl22-like1 (Rpl22l1) as a candidate. Rpl22l1 encodes a 122 amino acid protein that is 73% identical to Rpl22 (Figure 1A). The protein sequence of Rpl22l1 is highly conserved from human to zebrafish (Figure S5). To determine if significant levels of Rpl22l1 mRNA exists in tissues from Rpl22+/+ mice and whether Rpl22l1 transcript levels increase in Rpl22−/− mice, lung, liver, spleen and kidney were harvested from Rpl22−/− mice and their littermate controls and analyzed by quantitative RT-PCR (qRT-PCR) for Rpl22 and Rpl22l1 expression with Acidic Ribosomal Protein (ARBP) mRNA levels used for normalization (Figure 1B). In Rpl22+/+ samples, high Rpl22 expression was detected, while Rpl22l1 transcripts were less abundant. In samples isolated from Rpl22−/− mice, qRT-PCR revealed a ∼3-fold induction of Rpl22l1 mRNA expression relative to littermate controls.

Bottom Line: 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.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.

View Article: PubMed Central - PubMed

Affiliation: Department of Biochemistry, University of Washington, Seattle, Washington, United States of America.

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.

Show MeSH
Related in: MedlinePlus