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Assembly of the Human Signal Recognition Particle

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Non-Protein Coding RNAs

Part of the book series: Springer Series in Biophysics ((BIOPHYSICS,volume 13))

Large RNA-protein complexes (ribonucleoprotein particles or RNPs) control fundamental biological processes. Their correct assembly is essential for function and occurs by the ordered addition of proteins to the RNA. A good model system for studying RNP assembly is provided by the Signal Recognition Particle (SRP), an RNP conserved from bacteria to humans, with different degrees of complexity. Human SRP, composed of a single RNA molecule and six pro teins, is responsible for the co-translational targeting of secretory and membrane proteins to the endoplasmic reticulum membrane. In vitro studies reveal that the SRP proteins need to be added to the RNA sequentially. If the order of addition is altered, non-native particles are formed. The sequential association of proteins causes conformational changes in the RNA, allowing binding of other proteins. The in vivo assembly is regulated by the translocation of precursors between different cellular compartments. In this chapter we review the current understanding of the human SRP assembly mechanism.

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Abbreviations

EM:

electron microscopy

ER:

endoplasmic reticulum

Ffh:

fifty four homolog

GFP:

green fluorescent protein

GTP:

guanosine triphosphate

GTPase:

gua-nosine triphosphatase

RNC:

ribosome-nascent-chain

RNP:

ribonucleoprotein

rRNA:

ribosomal RNA

SR SRP:

receptor

SS:

signal sequence

SRP:

signal recognition particle

References

  • Althoff S, Selinger D, Wise JA (1994) Molecular evolution of SRP cycle components: functional implications. Nucleic Acids Res 22:1933–1947

    Article  Google Scholar 

  • Andersen JS, Lyon CE, Fox AH, Leung AK, Lam YW, Steen H, Mann M, Lamond AI (2002) Directed proteomic analysis of the human nucleolus. Curr Biol 12:1–11

    Article  Google Scholar 

  • Andreazzoli M, Gerbi SA (1991) Changes in 7SL RNA conformation during the signal recognition particle cycle. EMBO J 10:767–777

    Google Scholar 

  • Bernstein HD, Zopf D, Freymann DM, Walter P (1993) Functional substitution of the signal rec ognition particle 54-kDa subunit by its Escherichia coli homolog. Proc Natl Acad Sci U S A 90:5229–5233

    Article  ADS  Google Scholar 

  • Chen Y, Sinha K, Perumal K, Gu J, Reddy R (1998) Accurate 3′ end processing and adenylation of human signal recognition particle RNA and Alu RNA in vitro. J Biol Chem 273:35023–35031

    Article  Google Scholar 

  • Clerico EM, Maki JL, Gierasch LM (2008) Use of synthetic signal sequences to explore the pro tein export machinery. Biopolymers 90:307–319

    Article  Google Scholar 

  • Doudna JA, Batey RT (2004) Structural insights into the signal recognition particle. Annu Rev Biochem 73:539–557

    Article  Google Scholar 

  • Egea PF, Stroud RM, Walter P (2005) Targeting proteins to membranes: structure of the signal recognition particle. Curr Opin Struct Biol 15:213–220

    Article  Google Scholar 

  • Grosshans H, Deinert K, Hurt E, Simos G (2001) Biogenesis of the signal recognition particle (SRP) involves import of SRP proteins into the nucleolus, assembly with the SRP-RNA, and Xpo1p-mediated export. J Cell Biol 153:745–762

    Article  Google Scholar 

  • Hainzl T, Huang S, Sauer-Eriksson AE (2002) Structure of the SRP19 RNA complex and implications for signal recognition particle assembly. Nature 417:767–771

    Article  ADS  Google Scholar 

  • Halic M, Becker T, Pool MR, Spahn CM, Grassucci RA, Frank J, Beckmann R (2004) Structure of the signal recognition particle interacting with the elongation-arrested ribosome. Nature 427:808–814

    Article  ADS  Google Scholar 

  • He XP, Bataille N, Fried HM (1994) Nuclear export of signal recognition particle RNA is a facili tated process that involves the Alu sequence domain. J Cell Sci 107(Pt 4):903–912

    Google Scholar 

  • Herz J, Flint N, Stanley K, Frank R, Dobberstein B (1990) The 68 kDa protein of signal recognition particle contains a glycine-rich region also found in certain RNA-binding proteins. FEBS Lett 276:103–107

    Article  Google Scholar 

  • Huck L, Scherrer A, Terzi L, Johnson AE, Bernstein HD, Cusack S, Weichenrieder O, Strub K (2004) Conserved tertiary base pairing ensures proper RNA folding and efficient assembly of the signal recognition particle Alu domain. Nucleic Acids Res 32:4915–4924

    Article  Google Scholar 

  • Iakhiaeva E, Yin J, Zwieb C (2005) Identification of an RNA-binding domain in human SRP72. J Mol Biol 345:659–666

    Article  Google Scholar 

  • Jacobson MR, Pederson T (1998) Localization of signal recognition particle RNA in the nucleolus of mammalian cells. Proc Natl Acad Sci U S A 95:7981–7986

    Article  ADS  Google Scholar 

  • Janiak F, Walter P, Johnson AE (1992) Fluorescence-detected assembly of the signal recognition particle: binding of the two SRP protein heterodimers to SRP RNA is noncooperative. Biochemistry 31:5830–5840

    Article  Google Scholar 

  • Keenan RJ, Freymann DM, Stroud RM, Walter P (2001) The signal recognition particle. Annu Rev Biochem 70:755–775

    Article  Google Scholar 

  • Krieg UC, Walter P, Johnson AE (1986) Photocrosslinking of the signal sequence of nascent pre-prolactin to the 54-kilodalton polypeptide of the signal recognition particle. Proc Natl Acad Sci U S A 83:8604–8608

    Article  ADS  Google Scholar 

  • Kuglstatter A, Oubridge C, Nagai K (2002) Induced structural changes of 7SL RNA during the assembly of human signal recognition particle. Nat Struct Biol 9:740–744

    Article  Google Scholar 

  • Kurzchalia TV, Wiedmann M, Girshovich AS, Bochkareva ES, Bielka H, Rapoport TA (1986) The signal sequence of nascent preprolactin interacts with the 54K polypeptide of the signal rec ognition particle. Nature 320:634–636

    Article  ADS  Google Scholar 

  • Lentzen G, Moine H, Ehresmann C, Ehresmann B, Wintermeyer W (1996) Structure of 4.5S RNA in the signal recognition particle of Escherichia coli as studied by enzymatic and chemical probing. RNA 2:244–253

    Google Scholar 

  • Luirink J, Sinning I (2004) SRP-mediated protein targeting: structure and function revisited. Biochim Biophys Acta 1694:17–35

    Google Scholar 

  • Lütcke H (1995) Signal recognition particle (SRP), a ubiquitous initiator of protein translocation. Eur J Biochem 228:531–550

    Article  Google Scholar 

  • Lütcke H, High S, Romisch K, Ashford AJ, Dobberstein B (1992) The methionine-rich domain of the 54 kDa subunit of signal recognition particle is sufficient for the interaction with signal sequences. EMBO J 11:1543–1551

    Google Scholar 

  • Lütcke H, Prehn S, Ashford AJ, Remus M, Frank R, Dobberstein B (1993) Assembly of the 68-and 72-kD proteins of signal recognition particle with 7S RNA. J Cell Biol 121:977–985

    Article  Google Scholar 

  • Maity TS, Weeks KM (2007) A threefold RNA-protein interface in the signal recognition particle gates native complex assembly. J Mol Biol 369:512–524

    Article  Google Scholar 

  • Menichelli E, Isel C, Oubridge C, Nagai K (2007) Protein-induced conformational changes of RNA during the assembly of human signal recognition particle. J Mol Biol 367:187–203

    Article  Google Scholar 

  • Nagai K, Oubridge C, Kuglstatter A, Menichelli E, Isel C, Jovine L (2003) Structure, function and evolution of the signal recognition particle. EMBO J 22:3479–3485

    Article  Google Scholar 

  • Oubridge C, Kuglstatter A, Jovine L, Nagai K (2002) Crystal structure of SRP19 in complex with the S domain of SRP RNA and its implication for the assembly of the signal recognition parti cle. Mol Cell 9:1251–1261

    Article  Google Scholar 

  • Oubridge C, Isel C, Kuglstatter A, Nagai H (2003) Reply to “complex formations and crystal contacts”. Nat Struct Biol 10:494–495

    Article  Google Scholar 

  • Pederson T (1998) The plurifunctional nucleolus. Nucleic Acids Res 26:3871–3876

    Article  Google Scholar 

  • Politz JC, Yarovoi S, Kilroy SM, Gowda K, Zwieb C, Pederson T (2000) Signal recognition parti cle components in the nucleolus. Proc Natl Acad Sci U S A 97:55–60

    Article  ADS  Google Scholar 

  • Poritz MA, Bernstein HD, Strub K, Zopf D, Wilhelm H, Walter P (1990) An E. coli ribonucleo-protein containing 4.5S RNA resembles mammalian signal recognition particle. Science 250:1111–1117

    Article  ADS  Google Scholar 

  • Pool MR, Stumm J, Fulga TA, Sinning I, Dobberstein B (2002) Distinct modes of signal recognition particle interaction with the ribosome. Science 297:1345–1348

    Article  ADS  Google Scholar 

  • Romisch K, Webb J, Lingelbach K, Gausepohl H, Dobberstein B (1990) The 54-kD protein of signal recognition particle contains a methionine-rich RNA binding domain. J Cell Biol 111:1793–1802

    Article  Google Scholar 

  • Rose MA, Weeks KM (2001) Visualizing induced fit in early assembly of the human signal rec ognition particle. Nat Struct Biol 8:515–520

    Article  Google Scholar 

  • Scoulica E, Krause E, Meese K, Dobberstein B (1987) Disassembly and domain structure of the proteins in the signal-recognition particle. Eur J Biochem 163:519–528

    Article  Google Scholar 

  • Schwartz T, Blobel G (2003) Structural basis for the function of the beta subunit of the eukaryotic signal recognition particle receptor. Cell 112:793–803

    Article  Google Scholar 

  • Siegel V, Walter P (1986) Removal of the Alu structural domain from signal recognition particle leaves its protein translocation activity intact. Nature 320:81–84

    Article  ADS  Google Scholar 

  • Siegel V, Walter P (1988) Binding sites of the 19-kDa and 68/72-kDa signal recognition particle (SRP) proteins on SRP RNA as determined in protein-RNA “footprinting”. Proc Natl Acad Sci U S A 85:1801–1805

    Article  ADS  Google Scholar 

  • Sinha K, Perumal K, Chen Y, Reddy R (1999) Post-transcriptional adenylation of signal recognition particle RNA is carried out by an enzyme different from mRNA Poly(A) polymerase. J Biol Chem 274:30826–30831

    Article  Google Scholar 

  • Strub K, Walter P (1990) Assembly of the Alu domain of the signal recognition particle (SRP): dimerization of the two protein components is required for efficient binding to SRP RNA. Mol Cell Biol 10:777–784

    Google Scholar 

  • Talkington MW, Siuzdak G, Williamson JR (2005) An assembly landscape for the 30S ribosomal subunit. Nature 438:628–632

    Article  ADS  Google Scholar 

  • Terzi L, Pool MR, Dobberstein B, Strub K (2004) Signal recognition particle Alu domain occupies a defined site at the ribosomal subunit interface upon signal sequence recognition. Biochemistry 43:107–117

    Article  Google Scholar 

  • Walter P, Blobel G (1983) Disassembly and reconstitution of signal recognition particle. Cell 34:525–533

    Article  Google Scholar 

  • Weichenrieder O, Kapp U, Cusack S, Strub K (1997) Identification of a minimal Alu RNA folding domain that specifically binds SRP9/14. RNA 3:1262–1274

    Google Scholar 

  • Weichenrieder O, Wild K, Strub K, Cusack S (2000) Structure and assembly of the Alu domain of the mammalian signal recognition particle. Nature 408:167–173

    Article  ADS  Google Scholar 

  • Weichenrieder O, Stehlin C, Kapp U, Birse DE, Timmins PA, Strub K, Cusack S (2001) Hierarchical assembly of the Alu domain of the mammalian signal recognition particle. RNA 7:731–740

    Article  Google Scholar 

  • Yin J, Iakhiaeva E, Menichelli E, Zwieb C (2007) Identification of the RNA binding regions of SRP68/72 and SRP72 by systematic mutagenesis of human SRP RNA. RNA Biol 4(3):154–159

    Google Scholar 

  • Zieve G, Benecke BJ, Penman S (1977) Synthesis of two classes of small RNA species in vivo and in vitro. Biochemistry 16:4520–4525

    Article  Google Scholar 

  • Zopf D, Bernstein HD, Johnson AE, Walter P (1990) The methionine-rich domain of the 54 kD protein subunit of the signal recognition particle contains an RNA binding site and can be crosslinked to a signal sequence. EMBO J 9:4511–4517

    Google Scholar 

  • Zopf D, Bernstein HD, Walter P (1993) GTPase domain of the 54-kD subunit of the mammalian signal recognition particle is required for protein translocation but not for signal sequence binding. J Cell Biol 120:1113–1121

    Article  Google Scholar 

  • Zwieb C, Larsen N (1997) The Signal Recognition Particle Database (SRPDB). Nucleic Acids Res 25:107–108

    Article  Google Scholar 

  • Zwieb C, Muller F, Larsen N (1996) Comparative analysis of tertiary structure elements in signal recognition particle RNA. Fold Des 1:315–324

    Article  Google Scholar 

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Correspondence to Kiyoshi Nagai .

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Menichelli, E., Nagai, K. (2009). Assembly of the Human Signal Recognition Particle. In: Walter, N.G., Woodson, S.A., Batey, R.T. (eds) Non-Protein Coding RNAs. Springer Series in Biophysics, vol 13. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-540-70840-7_13

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