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Insights into the origin of the nuclear localization signals in conserved ribosomal proteins.

Melnikov S, Ben-Shem A, Yusupova G, Yusupov M - Nat Commun (2015)

Bottom Line: Eukaryotic ribosomal proteins, unlike their bacterial homologues, possess nuclear localization signals (NLSs) to enter the cell nucleus during ribosome assembly.Here we provide a comprehensive comparison of bacterial and eukaryotic ribosomes to show that NLSs appear in conserved ribosomal proteins via remodelling of their RNA-binding domains.This finding enabled us to identify previously unknown NLSs in ribosomal proteins from humans, and suggests that, apart from promoting protein transport, NLSs may facilitate folding of ribosomal RNA.

View Article: PubMed Central - PubMed

Affiliation: 1] Strasbourg University, 4 Rue Blaise Pascal, 67081 Strasbourg, France [2] Institute of Genetics and Molecular and Cellular Biology, 1 Rue Laurent Fries, 67400 Illkirch-Graffenstaden, France [3] Department of Molecular Biophysics and Biochemistry, Yale University, 266 Whitney Avenue, New Haven, Connecticut 06511, USA.

ABSTRACT
Eukaryotic ribosomal proteins, unlike their bacterial homologues, possess nuclear localization signals (NLSs) to enter the cell nucleus during ribosome assembly. Here we provide a comprehensive comparison of bacterial and eukaryotic ribosomes to show that NLSs appear in conserved ribosomal proteins via remodelling of their RNA-binding domains. This finding enabled us to identify previously unknown NLSs in ribosomal proteins from humans, and suggests that, apart from promoting protein transport, NLSs may facilitate folding of ribosomal RNA.

No MeSH data available.


Related in: MedlinePlus

Mapping nuclear/nucleolar localization signals (NLSs) within the ribosome structure reveals their common structural features and provides an insight into their evolutionary origin.(a) Crystal structures of four pairs of homologous proteins from 70S E. coli and 80S S. cerevisiae ribosomes: proteins are coloured according to the secondary structure, with red colour and red arrows pointing to NLSs of eukaryotic proteins (top panels) and to corresponding positions in bacterial homologues (bottom panels). NLSs reside within non-globular extensions of eukaryotic proteins with substantially remodelled secondary and tertiary structure compared with analogous protein segments in bacterial ribosomal proteins. (b) Fragments of the ribosome interior with a zoom on interactions between NLSs and rRNA within the eukaryotic ribosome (top panels) and corresponding segments of bacterial ribosome structure (bottom panels); nucleotides, which contact ribosomal proteins and ions/water molecules (shown as spheres), are in blue; labels correspond to 23S/25S rRNA helices. When ribosomal proteins are incorporated into the ribosome, NLSs are buried in the rRNA: compared with bacterial ribosomes, NLSs structurally replace non-globular extensions of bacterial proteins or magnesium ions/water in the ribosome interior and form similar stabilizing contacts with single-stranded helical junctions of conserved rRNA, suggesting a role of NLSs in rRNA folding.
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f1: Mapping nuclear/nucleolar localization signals (NLSs) within the ribosome structure reveals their common structural features and provides an insight into their evolutionary origin.(a) Crystal structures of four pairs of homologous proteins from 70S E. coli and 80S S. cerevisiae ribosomes: proteins are coloured according to the secondary structure, with red colour and red arrows pointing to NLSs of eukaryotic proteins (top panels) and to corresponding positions in bacterial homologues (bottom panels). NLSs reside within non-globular extensions of eukaryotic proteins with substantially remodelled secondary and tertiary structure compared with analogous protein segments in bacterial ribosomal proteins. (b) Fragments of the ribosome interior with a zoom on interactions between NLSs and rRNA within the eukaryotic ribosome (top panels) and corresponding segments of bacterial ribosome structure (bottom panels); nucleotides, which contact ribosomal proteins and ions/water molecules (shown as spheres), are in blue; labels correspond to 23S/25S rRNA helices. When ribosomal proteins are incorporated into the ribosome, NLSs are buried in the rRNA: compared with bacterial ribosomes, NLSs structurally replace non-globular extensions of bacterial proteins or magnesium ions/water in the ribosome interior and form similar stabilizing contacts with single-stranded helical junctions of conserved rRNA, suggesting a role of NLSs in rRNA folding.

Mentions: To gain an insight into the evolutionary origin of the NLSs in ribosomal proteins, we first mapped previously identified NLSs in the crystal structure of the eukaryotic ribosome from budding yeast Saccharomyces cerevisiae (S. cerevisiae), analysed their structure, and compared them to the corresponding segments in homologous proteins from the Escherichia coli (E. coli) ribosome (Methods). In total, we analysed twelve NLSs from ten conserved ribosomal proteins (Supplementary Table 1)25678910111213. We found both that all the NLSs of ribosomal proteins reside within non-globular extensions of rRNA-binding domains and that these NLS-carrying extensions have different structures in eukaryotes and in bacteria. For instance, NLSs of eukaryotic proteins uS3, uS4, uL13, uL15 and uL18 reside within the extensions that overlap with those of bacterial proteins, but adopt different secondary and tertiary structures (Fig. 1a, Supplementary Fig. 1). This finding was surprising, both because these extensions have similar size and charge in bacteria and eukaryotes and were previously assigned as conserved, according to sequence alignments141516. Other NLSs reside within rRNA-binding extensions that are absent in bacterial proteins – as sequence alignments had shown for proteins uS8, uL3 (ref. 2), uL18 (ref. 6), uL23 (ref. 13) and uL29 (ref. 7; (Fig. 1a, Supplementary Fig. 1). Taken together, this comparison illustrated that, despite high content of basic residues in ribosomal proteins, particularly at their rRNA-binding interface, the NLSs or similar motifs are absent in bacteria and apparently emerged via remodelling of the rRNA-binding domains of conserved ribosomal proteins.


Insights into the origin of the nuclear localization signals in conserved ribosomal proteins.

Melnikov S, Ben-Shem A, Yusupova G, Yusupov M - Nat Commun (2015)

Mapping nuclear/nucleolar localization signals (NLSs) within the ribosome structure reveals their common structural features and provides an insight into their evolutionary origin.(a) Crystal structures of four pairs of homologous proteins from 70S E. coli and 80S S. cerevisiae ribosomes: proteins are coloured according to the secondary structure, with red colour and red arrows pointing to NLSs of eukaryotic proteins (top panels) and to corresponding positions in bacterial homologues (bottom panels). NLSs reside within non-globular extensions of eukaryotic proteins with substantially remodelled secondary and tertiary structure compared with analogous protein segments in bacterial ribosomal proteins. (b) Fragments of the ribosome interior with a zoom on interactions between NLSs and rRNA within the eukaryotic ribosome (top panels) and corresponding segments of bacterial ribosome structure (bottom panels); nucleotides, which contact ribosomal proteins and ions/water molecules (shown as spheres), are in blue; labels correspond to 23S/25S rRNA helices. When ribosomal proteins are incorporated into the ribosome, NLSs are buried in the rRNA: compared with bacterial ribosomes, NLSs structurally replace non-globular extensions of bacterial proteins or magnesium ions/water in the ribosome interior and form similar stabilizing contacts with single-stranded helical junctions of conserved rRNA, suggesting a role of NLSs in rRNA folding.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4490412&req=5

f1: Mapping nuclear/nucleolar localization signals (NLSs) within the ribosome structure reveals their common structural features and provides an insight into their evolutionary origin.(a) Crystal structures of four pairs of homologous proteins from 70S E. coli and 80S S. cerevisiae ribosomes: proteins are coloured according to the secondary structure, with red colour and red arrows pointing to NLSs of eukaryotic proteins (top panels) and to corresponding positions in bacterial homologues (bottom panels). NLSs reside within non-globular extensions of eukaryotic proteins with substantially remodelled secondary and tertiary structure compared with analogous protein segments in bacterial ribosomal proteins. (b) Fragments of the ribosome interior with a zoom on interactions between NLSs and rRNA within the eukaryotic ribosome (top panels) and corresponding segments of bacterial ribosome structure (bottom panels); nucleotides, which contact ribosomal proteins and ions/water molecules (shown as spheres), are in blue; labels correspond to 23S/25S rRNA helices. When ribosomal proteins are incorporated into the ribosome, NLSs are buried in the rRNA: compared with bacterial ribosomes, NLSs structurally replace non-globular extensions of bacterial proteins or magnesium ions/water in the ribosome interior and form similar stabilizing contacts with single-stranded helical junctions of conserved rRNA, suggesting a role of NLSs in rRNA folding.
Mentions: To gain an insight into the evolutionary origin of the NLSs in ribosomal proteins, we first mapped previously identified NLSs in the crystal structure of the eukaryotic ribosome from budding yeast Saccharomyces cerevisiae (S. cerevisiae), analysed their structure, and compared them to the corresponding segments in homologous proteins from the Escherichia coli (E. coli) ribosome (Methods). In total, we analysed twelve NLSs from ten conserved ribosomal proteins (Supplementary Table 1)25678910111213. We found both that all the NLSs of ribosomal proteins reside within non-globular extensions of rRNA-binding domains and that these NLS-carrying extensions have different structures in eukaryotes and in bacteria. For instance, NLSs of eukaryotic proteins uS3, uS4, uL13, uL15 and uL18 reside within the extensions that overlap with those of bacterial proteins, but adopt different secondary and tertiary structures (Fig. 1a, Supplementary Fig. 1). This finding was surprising, both because these extensions have similar size and charge in bacteria and eukaryotes and were previously assigned as conserved, according to sequence alignments141516. Other NLSs reside within rRNA-binding extensions that are absent in bacterial proteins – as sequence alignments had shown for proteins uS8, uL3 (ref. 2), uL18 (ref. 6), uL23 (ref. 13) and uL29 (ref. 7; (Fig. 1a, Supplementary Fig. 1). Taken together, this comparison illustrated that, despite high content of basic residues in ribosomal proteins, particularly at their rRNA-binding interface, the NLSs or similar motifs are absent in bacteria and apparently emerged via remodelling of the rRNA-binding domains of conserved ribosomal proteins.

Bottom Line: Eukaryotic ribosomal proteins, unlike their bacterial homologues, possess nuclear localization signals (NLSs) to enter the cell nucleus during ribosome assembly.Here we provide a comprehensive comparison of bacterial and eukaryotic ribosomes to show that NLSs appear in conserved ribosomal proteins via remodelling of their RNA-binding domains.This finding enabled us to identify previously unknown NLSs in ribosomal proteins from humans, and suggests that, apart from promoting protein transport, NLSs may facilitate folding of ribosomal RNA.

View Article: PubMed Central - PubMed

Affiliation: 1] Strasbourg University, 4 Rue Blaise Pascal, 67081 Strasbourg, France [2] Institute of Genetics and Molecular and Cellular Biology, 1 Rue Laurent Fries, 67400 Illkirch-Graffenstaden, France [3] Department of Molecular Biophysics and Biochemistry, Yale University, 266 Whitney Avenue, New Haven, Connecticut 06511, USA.

ABSTRACT
Eukaryotic ribosomal proteins, unlike their bacterial homologues, possess nuclear localization signals (NLSs) to enter the cell nucleus during ribosome assembly. Here we provide a comprehensive comparison of bacterial and eukaryotic ribosomes to show that NLSs appear in conserved ribosomal proteins via remodelling of their RNA-binding domains. This finding enabled us to identify previously unknown NLSs in ribosomal proteins from humans, and suggests that, apart from promoting protein transport, NLSs may facilitate folding of ribosomal RNA.

No MeSH data available.


Related in: MedlinePlus