Abstract
Over the last five years Sm-like (Lsm) proteins have emerged as important players in many aspects of RNA metabolism, including splicing, nuclear RNA processing and messenger RNA decay. However, their precise function in these pathways remains somewhat obscure. In contrast, the role of the bacterial Lsm protein Hfq, which bears striking similarities in both structure and function to Lsm proteins, is much better characterized. In this perspective, we have highlighted several functions that Hfq shares with Lsm proteins and put forward hypotheses based on parallels between the two that might further the understanding of Lsm function.
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References
Salgado-Garrido, J., Bragado-Nilsson, E., Kandels-Lewis, S. & Seraphin, B. Sm and Sm-like proteins assemble in two related complexes of deep evolutionary origin. EMBO J. 18, 3451–3462 (1999).
Moller, T. et al. Hfq: a bacterial Sm-like protein that mediates RNA-RNA interaction. Mol. Cell 9, 23–30 (2002).
Zhang, A., Wassarman, K.M., Ortega, J., Steven, A.C. & Storz, G. The Sm-like Hfq protein increases OxyS RNA interaction with target mRNAs. Mol. Cell 9, 11–22 (2002).
Lerner, M.R. & Steitz, J.A. Antibodies to small nuclear RNAs complexed with proteins are produced by patients with systemic lupus erythematosus. Proc. Natl. Acad. Sci. USA 76, 5495–5499 (1979).
Hermann, H. et al. snRNP Sm proteins share two evolutionarily conserved sequence motifs which are involved in Sm protein-protein interactions. EMBO J. 14, 2076–2088 (1995).
Kambach, C. et al. Crystal structures of two Sm protein complexes and their implications for the assembly of the spliceosomal snRNPs. Cell 96, 375–387 (1999).
Albrecht, M. & Lengauer, T. Novel Sm-like proteins with long C-terminal tails and associated methyltransferases. FEBS Lett. 569, 18–26 (2004).
Khusial, P., Plaag, R. & Zieve, G.W. LSm proteins form heptameric rings that bind to RNA via repeating motifs. Trends Biochem. Sci. 30, 522–528 (2005).
Tharun, S. et al. Yeast Sm-like proteins function in mRNA decapping and decay. Nature 404, 515–518 (2000).
Tomasevic, N. & Peculis, B.A. Xenopus LSm proteins bind U8 snoRNA via an internal evolutionarily conserved octamer sequence. Mol. Cell. Biol. 22, 4101–4112 (2002).
Fernandez, C.F., Pannone, B.K., Chen, X., Fuchs, G. & Wolin, S.L. An Lsm2-Lsm7 complex in Saccharomyces cerevisiae associates with the small nucleolar RNA snR5. Mol. Biol. Cell 15, 2842–2852 (2004).
Pillai, R.S., Will, C.L., Luhrmann, R., Schumperli, D. & Muller, B. Purified U7 snRNPs lack the Sm proteins D1 and D2 but contain Lsm10, a new 14 kDa Sm D1-like protein. EMBO J. 20, 5470–5479 (2001).
Zaric, B. et al. Reconstitution of two recombinant LSm protein complexes reveals aspects of their architecture, assembly, and function. J. Biol. Chem. 280, 16066–16075 (2005).
Nikulin, A. et al. Structure of Pseudomonas aeruginosa Hfq protein. Acta Crystallogr. D 61, 141–146 (2005).
Sauter, C., Basquin, J. & Suck, D. Sm-like proteins in Eubacteria: the crystal structure of the Hfq protein from Escherichia coli. Nucleic Acids Res. 31, 4091–4098 (2003).
Schumacher, M.A., Pearson, R.F., Moller, T., Valentin-Hansen, P. & Brennan, R.G. Structures of the pleiotropic translational regulator Hfq and an Hfq-RNA complex: a bacterial Sm-like protein. EMBO J. 21, 3546–3556 (2002).
Franze de Fernandez, M.T., Eoyang, L. & August, J.T. Factor fraction required for the synthesis of bacteriophage Qbeta-RNA. Nature 219, 588–590 (1968).
Muffler, A., Fischer, D. & Hengge-Aronis, R. The RNA-binding protein HF-I, known as a host factor for phage Qbeta RNA replication, is essential for rpoS translation in Escherichia coli. Genes Dev. 10, 1143–1151 (1996).
Drepper, T. et al. The Hfq-like protein NrfA of the phototrophic purple bacterium Rhodobacter capsulatus controls nitrogen fixation via regulation of nifA and anfA expression. FEMS Microbiol. Lett. 215, 221–227 (2002).
Kaminski, P.A., Desnoues, N. & Elmerich, C. The expression of nifA in Azorhizobium caulinodans requires a gene product homologous to Escherichia coli HF-I, an RNA-binding protein involved in the replication of phage Q beta RNA. Proc. Natl. Acad. Sci. USA 91, 4663–4667 (1994).
Gottesman, S. The small RNA regulators of Escherichia coli: roles and mechanisms. Annu. Rev. Microbiol. 58, 303–328 (2004).
Vytvytska, O., Moll, I. & Kaberdin, V.R., von Gabain, A. & Blasi, U. Hfq (HF1) stimulates ompA mRNA decay by interfering with ribosome binding. Genes Dev. 14, 1109–1118 (2000).
Vecerek, B., Moll, I. & Blasi, U. Translational autocontrol of the Escherichia coli hfq RNA chaperone gene. RNA 11, 976–984 (2005).
Folichon, M., Allemand, F., Regnier, P. & Hajnsdorf, E. Stimulation of poly(A) synthesis by Escherichia coli poly(A) polymerase I is correlated with Hfq binding to poly(A) tails. FEBS J. 272, 454–463 (2005).
Moll, I., Afonyushkin, T., Vytvytska, O., Kaberdin, V.R. & Blasi, U. Coincident Hfq binding and RNase E cleavage sites on mRNA and small regulatory RNAs. RNA 9, 1308–1314 (2003).
Hajnsdorf, E. & Regnier, P. Host factor Hfq of Escherichia coli stimulates elongation of poly(A) tails by poly(A) polymerase I. Proc. Natl. Acad. Sci. USA 97, 1501–1505 (2000).
Mikulecky, P.J. et al. Escherichia coli Hfq has distinct interaction surfaces for DsrA, rpoS and poly(A) RNAs. Nat. Struct. Mol. Biol. 11, 1206–1214 (2004).
Moll, I., Leitsch, D., Steinhauser, T. & Blasi, U. RNA chaperone activity of the Sm-like Hfq protein. EMBO Rep. 4, 284–289 (2003).
Pruijn, G.J. Doughnuts dealing with RNA. Nat. Struct. Mol. Biol. 12, 562–564 (2005).
Achsel, T. et al. A doughnut-shaped heteromer of human Sm-like proteins binds to the 3′-end of U6 snRNA, thereby facilitating U4/U6 duplex formation in vitro. EMBO J. 18, 5789–5802 (1999).
Vidal, V.P., Verdone, L., Mayes, A.E. & Beggs, J.D. Characterization of U6 snRNA-protein interactions. RNA 5, 1470–1481 (1999).
Tharun, S. & Parker, R. Targeting an mRNA for decapping: displacement of translation factors and association of the Lsm1p-7p complex on deadenylated yeast mRNAs. Mol. Cell 8, 1075–1083 (2001).
Kufel, J., Bousquet-Antonelli, C., Beggs, J.D. & Tollervey, D. Nuclear pre-mRNA decapping and 5′ degradation in yeast require the Lsm2–8p complex. Mol. Cell. Biol. 24, 9646–9657 (2004).
Butland, G. et al. Interaction network containing conserved and essential protein complexes in Escherichia coli. Nature 433, 531–537 (2005).
Lehner, B. & Sanderson, C.M. A protein interaction framework for human mRNA degradation. Genome Res. 14, 1315–1323 (2004).
Giot, L. et al. A protein interaction map of Drosophila melanogaster. Science 302, 1727–1736 (2003).
Uetz, P. et al. A comprehensive analysis of protein-protein interactions in Saccharomyces cerevisiae. Nature 403, 623–627 (2000).
Ito, T. et al. A comprehensive two-hybrid analysis to explore the yeast protein interactome. Proc. Natl. Acad. Sci. USA 98, 4569–4574 (2001).
Ho, Y. et al. Systematic identification of protein complexes in Saccharomyces cerevisiae by mass spectrometry. Nature 415, 180–183 (2002).
Krogan, N.J. et al. High-definition macromolecular composition of yeast RNA-processing complexes. Mol. Cell 13, 225–239 (2004).
Gavin, A.C. et al. Functional organization of the yeast proteome by systematic analysis of protein complexes. Nature 415, 141–147 (2002).
Chang, T.C. et al. UNR, a new partner of poly(A)-binding protein, plays a key role in translationally coupled mRNA turnover mediated by the c-fos major coding-region determinant. Genes Dev. 18, 2010–2023 (2004).
Skabkina, O.V., Lyabin, D.N., Skabkin, M.A. & Ovchinnikov, L.P. YB-1 autoregulates translation of its own mRNA at or prior to the step of 40S ribosomal subunit joining. Mol. Cell. Biol. 25, 3317–3323 (2005).
Kushner, S.R. mRNA decay in Escherichia coli comes of age. J. Bacteriol. 184, 4658–4665 (2002).
Folichon, M. et al. The poly(A) binding protein Hfq protects RNA from RNase E and exoribonucleolytic degradation. Nucleic Acids Res. 31, 7302–7310 (2003).
Mohanty, B.K., Maples, V.F. & Kushner, S.R. The Sm-like protein Hfq regulates polyadenylation dependent mRNA decay in Escherichia coli. Mol. Microbiol. 54, 905–920 (2004).
Dreyfus, M. & Regnier, P. The poly(A) tail of mRNAs: bodyguard in eukaryotes, scavenger in bacteria. Cell 111, 611–613 (2002).
Wilusz, C.J., Wormington, M. & Peltz, S.W. The cap-to-tail guide to mRNA turnover. Nat. Rev. Mol. Cell Biol. 2, 237–246 (2001).
He, W. & Parker, R. The yeast cytoplasmic LsmI/Pat1p complex protects mRNA 3′ termini from partial degradation. Genetics 158, 1445–1455 (2001).
Kufel, J., Allmang, C., Petfalski, E., Beggs, J. & Tollervey, D. Lsm proteins are required for normal processing and stability of ribosomal RNAs. J. Biol. Chem. 278, 2147–2156 (2003).
Kufel, J., Allmang, C., Verdone, L., Beggs, J. & Tollervey, D. A complex pathway for 3′ processing of the yeast U3 snoRNA. Nucleic Acids Res. 31, 6788–6797 (2003).
Fromont-Racine, M. et al. Genome-wide protein interaction screens reveal functional networks involving Sm-like proteins. Yeast 17, 95–110 (2000).
Wyers, F. et al. Cryptic pol II transcripts are degraded by a nuclear quality control pathway involving a new poly(A) polymerase. Cell 121, 725–737 (2005).
LaCava, J. et al. RNA degradation by the exosome is promoted by a nuclear polyadenylation complex. Cell 121, 713–724 (2005).
Vanacova, S. et al. A new yeast poly(A) polymerase complex involved in RNA quality control. PLoS Biol. 3, e189 (2005).
Geissmann, T.A. & Touati, D. Hfq, a new chaperoning role: binding to messenger RNA determines access for small RNA regulator. EMBO J. 23, 396–405 (2004).
Schuppli, D. et al. Altered 3′-terminal RNA structure in phage Qbeta adapted to host factor-less Escherichia coli. Proc. Natl. Acad. Sci. USA 94, 10239–10242 (1997).
Verdone, L., Galardi, S., Page, D. & Beggs, J.D. Lsm proteins promote regeneration of pre-mRNA splicing activity. Curr. Biol. 14, 1487–1491 (2004).
Zhang, D., Abovich, N. & Rosbash, M. A biochemical function for the Sm complex. Mol. Cell 7, 319–329 (2001).
Afonyushkin, T., Vecerek, B., Moll, I., Blasi, U. & Kaberdin, V.R. Both RNase E and RNase III control the stability of sodB mRNA upon translational inhibition by the small regulatory RNA RyhB. Nucleic Acids Res. 33, 1678–1689 (2005).
Masse, E., Escorcia, F.E. & Gottesman, S. Coupled degradation of a small regulatory RNA and its mRNA targets in Escherichia coli. Genes Dev. 17, 2374–2383 (2003).
Zamore, P.D. & Haley, B. Ribo-gnome: the big world of small RNAs. Science 309, 1519–1524 (2005).
Cougot, N., Babajko, S. & Seraphin, B. Cytoplasmic foci are sites of mRNA decay in human cells. J. Cell Biol. 165, 31–40 (2004).
Ingelfinger, D., Arndt-Jovin, D.J., Luhrmann, R., & Achsel, T. The human LSm1–7 proteins colocalize with the mRNA-degrading enzymes Dcp1/2 and Xrnl in distinct cytoplasmic foci. RNA 8, 1489–1501 (2002).
Liu, J., Valencia-Sanchez, M.A., Hannon, G.J. & Parker, R. MicroRNA-dependent localization of targeted mRNAs to mammalian P-bodies. Nat. Cell Biol. 7, 719–723 (2005).
Sen, G.L. & Blau, H.M. Argonaute 2/RISC resides in sites of mammalian mRNA decay known as cytoplasmic bodies. Nat. Cell Biol. 7, 633–636 (2005).
Noueiry, A.O., Diez, J., Falk, S.P., Chen, J. & Ahlquist, P. Yeast Lsm1p-7p/Pat1p deadenylation-dependent mRNA-decapping factors are required for brome mosaic virus genomic RNA translation. Mol. Cell. Biol. 23, 4094–4106 (2003).
Noueiry, A.O. & Ahlquist, P. Brome mosaic virus RNA replication: revealing the role of the host in RNA virus replication. Annu. Rev. Phytopathol. 41, 77–98 (2003).
Diez, J., Ishikawa, M., Kaido, M. & Ahlquist, P. Identification and characterization of a host protein required for efficient template selection in viral RNA replication. Proc. Natl. Acad. Sci. USA 97, 3913–3918 (2000).
Liu, Q. et al. Identification and functional characterization of lsm proteins in Trypanosoma brucei. J. Biol. Chem. 279, 18210–18219 (2004).
Acknowledgements
We would like to thank our colleagues for stimulating discussions relating to this topic and apologize to the authors of studies that we were unable to cite owing to lack of space. We are grateful to O. Peersen for his help in generating the Hfq structure for Figure 1. Research in the Wilusz laboratory is supported by the US National Institutes of Health (grants GM072481, GM063832 and AI063434 to J.W.).
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Wilusz, C., Wilusz, J. Eukaryotic Lsm proteins: lessons from bacteria. Nat Struct Mol Biol 12, 1031–1036 (2005). https://doi.org/10.1038/nsmb1037
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DOI: https://doi.org/10.1038/nsmb1037
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