Abstract
The RNA chaperone Hfq is an important bacterial post-transcriptional regulator. Most studies on Hfq are focused on the role of this protein on small non-coding RNAs (sRNAs) and messenger RNAs (mRNAs). The most well-characterized function of Hfq is its role as RNA matchmaker, promoting the base-pairing between sRNAs and their mRNA targets. However, novel substrates and previous unrecognized functions of Hfq have now been identified, which expanded the regulatory spectrum of this protein. Hfq was recently found to bind rRNA and act as a new ribosome biogenesis factor, affecting rRNA processing, ribosome assembly, translational efficiency and translational fidelity. Hfq was also found to bind tRNAs, which could provide an additional mechanism for its role on the accuracy of protein synthesis. The list of substrates does not include RNA exclusively since Hfq was shown to bind DNA, playing an important role in DNA compaction. Additionally, Hfq is also capable to establish many protein–protein interactions. Overall, the functions of the RNA-binding protein Hfq have been expanded beyond its function in small RNA-mediated regulation. The identification of additional substrates and new functions provides alternative explanations for the importance of the chaperone Hfq as a global regulator.
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References
Andrade JM, Arraiano CM (2008) PNPase is a key player in the regulation of small RNAs that control the expression of outer membrane proteins. RNA 14:543–551. https://doi.org/10.1261/rna.683308
Andrade JM, Pobre V, Matos AM, Arraiano CM (2012) The crucial role of PNPase in the degradation of small RNAs that are not associated with Hfq. RNA 18:844–855. https://doi.org/10.1261/rna.029413.111
Andrade JM, Pobre V, Arraiano CM (2013) Small RNA modules confer different stabilities and interact differently with multiple targets. PLoS One 8:e52866. https://doi.org/10.1371/journal.pone.0052866
Andrade JM, dos Santos RF, Chelysheva I et al (2018) The RNA-binding protein Hfq is important for ribosome biogenesis and affects translation fidelity. EMBO J 37:e97631. https://doi.org/10.15252/embj.201797631
Azam TA, Ishihama A (1999) Twelve species of the nucleoid-associated protein from Escherichia coli. J Biol Chem 274:33105–33113. https://doi.org/10.1074/jbc.274.46.33105
Azam MS, Vanderpool CK (2018) Translational regulation by bacterial small RNAs via an unusual Hfq-dependent mechanism. Nucleic Acids Res 46:2585–2599. https://doi.org/10.1093/nar/gkx1286
Barrera I, Schuppli D, Sogo JM, Weber H (1993) Different mechanisms of recognition of bacteriophage Qβ plus and minus strand RNAs by Qβ replicase. J Mol Biol 232:512–521. https://doi.org/10.1006/jmbi.1993.1407
Beggs JD (2005) Lsm proteins and RNA processing. Biochem Soc Trans 33:433–438. https://doi.org/10.1042/BST0330433
Bidnenko E, Bidnenko V (2018) Transcription termination factor Rho and microbial phenotypic heterogeneity. Curr Genet 64:541–546. https://doi.org/10.1007/s00294-017-0775-7
Cai Q, Wang G, Li Z et al (2019) SWATH based quantitative proteomics analysis reveals Hfq2 play an important role on pleiotropic physiological functions in Aeromonas hydrophila. J Proteom 195:1–10. https://doi.org/10.1016/j.jprot.2018.12.030
Carmichael GG (1975) Isolation of bacterial and phage proteins by homopolymer RNA-cellulose chromatography. J Biol Chem 250:6160–6167
Cech GM, Szalewska-Pałasz A, Kubiak K et al (2016) The Escherichia coli Hfq protein: an unattended DNA-transactions regulator. Front Mol Biosci 3:36. https://doi.org/10.3389/fmolb.2016.00036
Chen J, Gottesman S (2017) Hfq links translation repression to stress-induced mutagenesis in E. coli. Genes Dev 31:1382–1395. https://doi.org/10.1101/gad.302547.117
Christiansen JK, Nielsen JS, Ebersbach T et al (2006) Identification of small Hfq-binding RNAs in Listeria monocytogenes. RNA 12:1383–1396. https://doi.org/10.1261/rna.49706
Collins BM, Harrop SJ, Kornfeld GD et al (2001) Crystal structure of a heptameric Sm-like protein complex from archaea: implications for the structure and evolution of snRNPs. J Mol Biol 309:915–923. https://doi.org/10.1006/jmbi.2001.4693
De Haseth PL, Uhlenbeck OC (1980) Interaction of Escherichia coli host factor protein with Q beta ribonucleic acid. Biochemistry 19:6146–6151. https://doi.org/10.1021/bi00567a030
Diestra E, Cayrol B, Arluison V, Risco C (2009) Cellular electron microscopy imaging reveals the localization of the Hfq protein close to the bacterial membrane. PLoS One 4:e8301. https://doi.org/10.1371/journal.pone.0008301
Eason IR, Kaur HP, Alexander KA, Sukhodolets MV (2019) Growth phase-specific changes in the composition of E. coli transcription complexes. J Chromatogr B Anal Technol Biomed Life Sci 1109:155–165. https://doi.org/10.1016/j.jchromb.2019.01.014
El Mouali Y, Balsalobre C (2019) 3′untranslated regions: regulation at the end of the road. Curr Genet 65:127–131. https://doi.org/10.1007/s00294-018-0877-x
Ellis MJ, Trussler RS, Haniford DB (2015) Hfq binds directly to the ribosome-binding site of IS 10 transposase mRNA to inhibit translation. Mol Microbiol 96:633–650. https://doi.org/10.1111/mmi.12961
Folichon M, Arluison V, Pellegrini O et al (2003) The poly(A) binding protein Hfq protects RNA from RNase E and exoribonucleolytic degradation. Nucleic Acids Res 31:7302–7310
Franze de Fernandez MT, Eoyang L, August JT (1968) Factor fraction required for the synthesis of bacteriophage Qbeta-RNA. Nature 219:588–590. https://doi.org/10.1038/219588a0
Franze de Fernandez MT, Hayward WS, August JT (1972) Bacterial proteins required for replication of phage Q ribonucleic acid. Purification and properties of host factor I, a ribonucleic acid-binding protein. J Biol Chem 247:824–831
Hajnsdorf E, Régnier P (2000) 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. https://doi.org/10.1073/pnas.040549897
Hämmerle H, Beich-Frandsen M, Večerek B et al (2012) Structural and biochemical studies on ATP binding and hydrolysis by the Escherichia coli RNA chaperone Hfq. PLoS One 7:e50892. https://doi.org/10.1371/journal.pone.0050892
Haniford DB, Ellis MJ (2015) Transposons Tn10 and Tn5. Microbiol Spectr 3(1). https://doi.org/10.1128/microbiolspec.MDNA3-0002-2014
Holmqvist E, Vogel J (2018) RNA-binding proteins in bacteria. Nat Rev Microbiol 16:601–615. https://doi.org/10.1038/s41579-018-0049-5
Jiang K, Zhang C, Guttula D et al (2015) Effects of Hfq on the conformation and compaction of DNA. Nucleic Acids Res 43:4332–4341. https://doi.org/10.1093/nar/gkv268
Kufel J, Allmang C, Verdone L et al (2002) Lsm Proteins are required for normal processing of Pre-tRNAs and their efficient association with La-homologous protein Lhp1p. Mol Cell Biol 22:5248–5256. https://doi.org/10.1128/MCB.22.14.5248-5256.2002
Kufel J, Allmang C, Petfalski E et al (2003) Lsm proteins are required for normal processing and stability of ribosomal RNAs. J Biol Chem 278:2147–2156. https://doi.org/10.1074/jbc.M208856200
Lawson MR, Berger JM (2019) Tuning the sequence specificity of a transcription terminator. Curr Genet. https://doi.org/10.1007/s00294-019-00939-1
Le Derout J, Folichon M, Briani F et al (2003) Hfq affects the length and the frequency of short oligo(A) tails at the 3′ end of Escherichia coli rpsO mRNAs. Nucleic Acids Res 31:4017–4023. https://doi.org/10.1093/nar/gkg456
Le Derout J, Boni IV, Régnier P, Hajnsdorf E (2010) Hfq affects mRNA levels independently of degradation. BMC Mol Biol 11:17. https://doi.org/10.1186/1471-2199-11-17
Lee T, Feig AL (2008) The RNA binding protein Hfq interacts specifically with tRNAs. RNA 14:514–523. https://doi.org/10.1261/rna.531408
Link TM, Valentin-Hansen P, Brennan RG (2009) Structure of Escherichia coli Hfq bound to polyriboadenylate RNA. Proc Natl Acad Sci USA 106:19292–19297. https://doi.org/10.1073/pnas.0908744106
Majdalani N, Chen S, Murrow J et al (2001) Regulation of RpoS by a novel small RNA: the characterization of RprA. Mol Microbiol 39:1382–1394. https://doi.org/10.1111/j.1365-2958.2001.02329.x
Malabirade A, Jiang K, Kubiak K et al (2017) Compaction and condensation of DNA mediated by the C-terminal domain of Hfq. Nucleic Acids Res 45:7299–7308. https://doi.org/10.1093/nar/gkx431
Malabirade A, Partouche D, El Hamoui O et al (2018) Revised role for Hfq bacterial regulator on DNA topology. Sci Rep 8:16792. https://doi.org/10.1038/s41598-018-35060-9
Masse E, Escorcia FE, Gottesman S (2003) Coupled degradation of a small regulatory RNA and its mRNA targets in Escherichia coli. Genes Dev 17:2374–2383. https://doi.org/10.1101/gad.1127103
Melamed S, Peer A, Faigenbaum-Romm R et al (2016) Global mapping of small RNA-target interactions in bacteria. Mol Cell 63:884–897. https://doi.org/10.1016/j.molcel.2016.07.026
Mohanty BK, Maples VF, Kushner SR (2004) The Sm-like protein Hfq regulates polyadenylation dependent mRNA decay in Escherichia coli. Mol Microbiol 54:905–920. https://doi.org/10.1111/j.1365-2958.2004.04337.x
Moll I, Leitsch D, Steinhauser T, Bläsi U (2003) RNA chaperone activity of the Sm-like Hfq protein. EMBO Rep 4:284–289. https://doi.org/10.1038/sj.embor.embor772
Morita T, Maki K, Aiba H (2005) RNase E-based ribonucleoprotein complexes: mechanical basis of mRNA destabilization mediated by bacterial noncoding RNAs. Genes Dev 19:2176–2186. https://doi.org/10.1101/gad.1330405
Morita T, Nishino R, Aiba H (2017) Role of the terminator hairpin in the biogenesis of functional Hfq-binding sRNAs. RNA 23:1419–1431. https://doi.org/10.1261/rna.060756.117
Rabhi M, Espéli O, Schwartz A et al (2011) The Sm-like RNA chaperone Hfq mediates transcription antitermination at Rho-dependent terminators. EMBO J 30:2805–2816. https://doi.org/10.1038/emboj.2011.192
Régnier P, Hajnsdorf E (2013) The interplay of Hfq, poly(A) polymerase I and exoribonucleases at the 3′ ends of RNAs resulting from Rho-independent termination: a tentative model. RNA Biol 10:602–609. https://doi.org/10.4161/rna.23664
Reichelt R, Grohmann D, Willkomm S (2018) A journey through the evolutionary diversification of archaeal Lsm and Hfq proteins. Emerg Top Life Sci 2:647–657. https://doi.org/10.1042/ETLS20180034
Rochat T, Delumeau O, Figueroa-Bossi N et al (2015) Tracking the elusive function of Bacillus subtilis Hfq. PLoS One 10:e0124977. https://doi.org/10.1371/journal.pone.0124977
Salvail H, Caron M-P, Bélanger J, Massé E (2013) Antagonistic functions between the RNA chaperone Hfq and an sRNA regulate sensitivity to the antibiotic colicin. EMBO J 32:2764–2778. https://doi.org/10.1038/emboj.2013.205
Santiago-Frangos A, Woodson SA (2018) Hfq chaperone brings speed dating to bacterial sRNA. Wiley Interdiscip Rev RNA 9:e1475. https://doi.org/10.1002/wrna.1475
Sauer E, Weichenrieder O (2011) Structural basis for RNA 3′-end recognition by Hfq. Proc Natl Acad Sci USA 108:13065–13070. https://doi.org/10.1073/pnas.1103420108
Sauer E, Schmidt S, Weichenrieder O (2012) Small RNA binding to the lateral surface of Hfq hexamers and structural rearrangements upon mRNA target recognition. Proc Natl Acad Sci USA 109:9396–9401. https://doi.org/10.1073/pnas.1202521109
Sauter C, Basquin J, Suck D (2003) Sm-like proteins in Eubacteria: the crystal structure of the Hfq protein from Escherichia coli. Nucleic Acids Res 31:4091–4098. https://doi.org/10.1093/nar/gkg480
Schu DJ, Zhang A, Gottesman S, Storz G (2015) Alternative Hfq-sRNA interaction modes dictate alternative mRNA recognition. EMBO J 34:2557–2573. https://doi.org/10.15252/embj.201591569
Schuppli D, Georgijevic J, Weber H (2000) Synergism of mutations in bacteriophage Qbeta RNA affecting host factor dependence of Qbeta replicase. J Mol Biol 295:149–154. https://doi.org/10.1006/jmbi.1999.3373
Sharma IM, Korman A, Woodson SA (2018) The Hfq chaperone helps the ribosome mature. EMBO J 37:e99616. https://doi.org/10.15252/embj.201899616
Smirnov A, Wang C, Drewry LL, Vogel J (2017) Molecular mechanism of mRNA repression in trans by a ProQ-dependent small RNA. EMBO J 36:1029–1045. https://doi.org/10.15252/embj.201696127
Soper T, Mandin P, Majdalani N et al (2010) Positive regulation by small RNAs and the role of Hfq. Proc Natl Acad Sci 107:9602–9607. https://doi.org/10.1073/pnas.1004435107
Strader MB, Hervey Iv WJ, Costantino N, Fujgaki S, Chen CY, Akal-Strader A, Ihunnah CA, Makusky AJ, Court D, Markey SP, Kowalak JA (2013) A coordinated proteomic approach for identifying proteins that interact with the E. coli ribosomal protein S12. J Proteome Res 12:1289–1299. https://doi.org/10.1021/pr3009435
Sukhodolets MV, Garges S (2003) Interaction of Escherichia coli RNA polymerase with the ribosomal protein S1 and the Sm-like ATPase Hfq. Biochemistry 42:8022–8034. https://doi.org/10.1021/bi020638i
Tsui HC, Leung HC, Winkler ME (1994) Characterization of broadly pleiotropic phenotypes caused by an hfq insertion mutation in Escherichia coli K-12. Mol Microbiol 13:35–49. https://doi.org/10.1111/j.1365-2958.1994.tb00400.x
Updegrove TB, Correia JJ, Galletto R et al (2010) E. coli DNA associated with isolated Hfq interacts with Hfq’s distal surface and C-terminal domain. Biochim Biophys Acta Gene Regul Mech 1799:588–596. https://doi.org/10.1016/j.bbagrm.2010.06.007
Updegrove TB, Zhang A, Storz G (2016) Hfq: the flexible RNA matchmaker. Curr Opin Microbiol 30:133–138. https://doi.org/10.1016/j.mib.2016.02.003
Valentin-Hansen P, Eriksen M, Udesen C (2004) The bacterial Sm-like protein Hfq: a key player in RNA transactions. Mol Microbiol 51:1525–1533. https://doi.org/10.1046/j.1365-2958.2003.03935.x
Vecerek B, Moll I, Bläsi U (2005) Translational autocontrol of the Escherichia coli hfq RNA chaperone gene. RNA 11:976–984. https://doi.org/10.1261/rna.2360205
Vogel J, Papenfort K (2006) Small non-coding RNAs and the bacterial outer membrane. Curr Opin Microbiol 9:605–611. https://doi.org/10.1016/j.mib.2006.10.006
Wassarman KM, Repoila F, Rosenow C et al (2001) Identification of novel small RNAs using comparative genomics and microarrays. Genes Dev 15:1637–1651. https://doi.org/10.1101/gad.901001
Wilusz CJ, Wilusz J (2013) Lsm proteins and Hfq: life at the 3′ end. RNA Biol 10:592–601. https://doi.org/10.4161/rna.23695
Woodson SA, Panja S, Santiago-Frangos A (2018) Proteins that chaperone RNA regulation. Microbiol Spectr 6:385–397. https://doi.org/10.1128/microbiolspec.RWR-0026-2018
Wroblewska Z, Olejniczak M (2016) Hfq assists small RNAs in binding to the coding sequence of ompD mRNA and in rearranging its structure. RNA 22:979–994. https://doi.org/10.1261/rna.055251.115
Zhang A, Wassarman KM, Rosenow C et al (2003) Global analysis of small RNA and mRNA targets of Hfq. Mol Microbiol 50:1111–1124. https://doi.org/10.1046/j.1365-2958.2003.03734.x
Acknowledgements
This work was financially supported by Project LISBOA-01-0145-FEDER-007660 (Microbiologia Molecular, Estrutural e Celular) funded by FEDER through COMPETE2020—Programa Operacional Competitividade e Internacionalização (POCI) and by FCT—Fundação para a Ciência e a Tecnologia (Portugal), including Grant PTDC/BIA-MIC/1399/2014 to CMA, Program IF (IF/00961/2014) and Grants PTDC/IMI-MIC/4463/2014 and PTDC/BIA-MIC/32525/2017 to JMA.
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dos Santos, R.F., Arraiano, C.M. & Andrade, J.M. New molecular interactions broaden the functions of the RNA chaperone Hfq. Curr Genet 65, 1313–1319 (2019). https://doi.org/10.1007/s00294-019-00990-y
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DOI: https://doi.org/10.1007/s00294-019-00990-y