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Review
. 2012 May 23;13(6):355-69.
doi: 10.1038/nrm3359.

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

Shifeng Xue  1 , Maria Barna
Affiliations
Review

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

Shifeng Xue et al. Nat Rev Mol Cell Biol. .

Abstract

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 how the genomic template is translated into functional proteins. Moreover, constitutive components of the ribosome may also exert more specialized activities by virtue of their interactions with specific mRNA regulatory elements such as internal ribosome entry sites (IRESs) or upstream open reading frames (uORFs). Here we discuss the hypothesis that intrinsic regulation by the ribosome acts to selectively translate subsets of mRNAs harbouring unique cis-regulatory elements, thereby introducing an additional level of regulation in gene expression and the life of an organism.

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Figures

Figure 1
Figure 1. Heterogeneity in the ribosome at the level of ribosomal protein composition and post-translational modifications across different species
a | Introns of genes encoding ribosomal proteins in Saccharomyces cerevisiae regulate the expression of both the intron-containing ribosomal protein genes and their paralogues, and this has important outcomes in cells: for example, increased fitness under stress. 70% of ribosomal protein paralogue pairs show differential expression. b | In plants, ribosomal protein paralogues have different functions and different expression patterns. For example, in Arabidopsis thaliana, RPS5A is expressed in rapidly dividing cells early in embryonic development, whereas RPS5B is expressed in cells undergoing differentiation. c | In Drosophila melanogaster, ribosomal protein paralogues show different expression patterns in the adult testes. For example, RPL22 is expressed ubiquitously, but RPL22-like protein levels are specifically increased in the testes. Both proteins are incorporated into translationally active ribosomes (called the polysomes). d | In humans, only some ribosomal protein paralogues have been identified; however, notable examples exist. RPS4Y1 is expressed ubiquitously, whereas RPS4Y2 is restricted to the testis and prostate. e | In the life cycle of the social amoebae Dictyostelium discoideum, ribosome switches are characterized by changes in ribosome composition at the level of ribosomal protein expression and post-translational modifications. For example, phosphorylation (P) on RPS19 and methylation (M) on RPL2 are lost as D. discoideum aggregates from a single cell amoebae to a multicellular fruiting body, while RPL20 gains phosphorylation marks. RPL18 is exclusively found in ribosomes of developing cells and not in those of the amoebae stage. f | In mice, the mRNA expression pattern of ribosomal proteins varies dramatically among tissues. This may potentially translate into unique ribosomal protein compositions of ribosomes in distinct cell types. Part a is modified, with permission, from REF. © (2011) Elsevier. Part b is modified, with permission, from REF. © (2001) The Company of Biologists. Part f is modified, with permission, from REF. © (2011) Elsevier.
Figure 2
Figure 2. Ribosome-associated factors affect ribosome function
a | In Drosophila melanogaster, Reaper protein associates with the 40S small ribosomal unit, disrupts the cap-scanning mechanism of translational initiation and promotes the translation of mRNAs containing internal ribosome entry site (IRES) elements that may be required for cell death. b | Ribosome-bound RACK1 can potentially localize ribosomes to the cell membrane by interacting with transmembrane receptors. RACK1 can recruit the microRNA (miRNA)-induced silencing complex (miRISC) to the ribosome to facilitate miRNA-mediated repression. RACK1 also binds to RNA-binding proteins such as yeast Scp160p, and this interaction may facilitate the recruitment of specific mRNAs to the ribosome.
Figure 3
Figure 3. rRNA heterogeneity
Plasmodium falciparum expresses different forms of ribosomal RNAs (rRNAs) when it is in sporozoite form (type S) in the mosquito and when it is in the asexual form (type A) in the bloodstream. The two forms of rRNA differ mainly in the variable regions . Chimeric yeast ribosomes in which part of the 25S rRNA was replaced with type S P. falciparum rRNA are non-functional, whereas replacement with type A P. falciparum rRNA does not produce any defects, suggesting the two types of rRNA are functionally distinct.
Figure 4
Figure 4. Cis-regulatory elements within mRNAs that interface with ribosomes or ribosomal proteins to confer transcript-specific regulation of gene expression
a | Internal ribosome entry site (IRES) elements: the ribosomal protein RPS25 is necessary for the recruitment of the small ribosomal subunit 40S to the cricket paralysis virus (CrPV) intergenic region IRES to initiate translational initiation by a cap-independent mechanism in yeast and mammals. Ribosomal RNA (rRNA) modifications (such as pseudouridylation (Ψ)) are important for ribosome binding to IRES elements. b | Upstream open reading frames (uORFs): RPL24 promotes the reinitiation of translation following an uORF, thereby allowing the translation of the downstream main ORF. m7G, 7-methylguanosine, UTR, untranslated region.
Figure 5
Figure 5. Ribosome specificity in cell and developmental biology
a | In Escherichia coli, MazF cleaves the 3′ end of the 16S ribosomal RNA (rRNA) and releases the anti-Shine-Dalgarno sequence, thereby generating specialized ribosomes that translate leaderless mRNAs that are involved in the stress response. b | Mitochondrial ribosomes (green) in the germ plasm (yellow area) of Drosophila melanogaster embryos are found outside of mitochondria and may translate certain cytoplasmic germ cell-specific mRNAs. c | Gene expression of Rpl38 (pink) is highly increased in somites and the neural tube of developing mouse embryos and is responsible for translating specific homeobox (Hox) mRNAs that are necessary for axial skeletal patterning and the specification of PEA3-expressing motor neurons. d | Localized translation takes place in dendrites, far away from the cell body. mRNAs for ribosomal proteins are found in dendrites and can potentially form dendrite-specific ribosomes.
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References

    1. Frank J. The ribosome — a macromolecular machine par excellence. Chem. Biol. 2000;7:R133–R141. - PubMed

    1. Sonenberg N, Hinnebusch AG. Regulation of translation initiation in eukaryotes: mechanisms and biological targets. Cell. 2009;136:731–745. Reviews the mechanism of translation initiation and its regulation..

    1. Alberts B. The cell as a collection of protein machines: preparing the next generation of molecular biologists. Cell. 1998;92:291–294. - PubMed
    1. Zaher HS, Green R. Fidelity at the molecular level: lessons from protein synthesis. Cell. 2009;136:746–762. - PMC - PubMed
    1. Warner JR. The economics of ribosome biosynthesis in yeast. Trends Biochem. Sci. 1999;24:437–440. - PubMed

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