Elsevier

Biochimie

Volume 164, September 2019, Pages 99-104
Biochimie

Mini-review
In vivo assembly of eukaryotic signal recognition particle: A still enigmatic process involving the SMN complex

https://doi.org/10.1016/j.biochi.2019.04.007Get rights and content

Highlights

  • SRP is crucial for protein targeting to the ER in eukaryotes and to the plasma membrane in archaea and bacteria.

  • SRP assembly is a stepwise process that occurs in the nucleolus and in the cytoplasm in eukaryotic cells.

  • The SMN complex is required for SRP assembly in eukaryotic cells.

Abstract

The signal recognition particle (SRP) is a universally conserved non-coding ribonucleoprotein complex that is essential for targeting transmembrane and secretory proteins to the endoplasmic reticulum. Its composition and size varied during evolution. In mammals, SRP contains one RNA molecule, 7SL RNA, and six proteins: SRP9, 14, 19, 54, 68 and 72. Despite a very good understanding of the SRP structure and of the SRP assembly in vitro, how SRP is assembled in vivo remains largely enigmatic. Here we review current knowledge on how the 7SL RNA is assembled with core proteins to form functional RNP particles in cells. SRP biogenesis is believed to take place both in the nucleolus and in the cytoplasm and to rely on the survival of motor neuron complex, whose defect leads to spinal muscular atrophy.

Section snippets

RNP biogenesis often requires numerous assembly factors

Molecular assemblies of biomolecules facilitate diverse biological tasks in the cells of all organisms. Many cellular functions are performed by a family of molecular machines made up of RNA-protein complexes, called non-coding ribonucleoprotein (ncRNP) complexes. These ncRNPs include ribosomes and spliceosomes, respectively involved in translation and splicing, and a plethora of other stable ncRNPs involved in multiple essential cellular functions including chromatin modification,

Signal recognition particle: composition and function in protein secretion

Protein secretion and their correct cellular localization are crucial to maintain cell compartmentalization and homeostasis. In eukaryotes, one third of proteins are translocated into the ER, prior to being transported to their final destinations. There are several strategies to localize proteins to the ER (for a recent review, see Ref. [16]); the principal and best characterized one relies on SRP, which is one of the most abundant ncRNPs in cells. It is conserved across all three kingdoms of

Signal recognition particle biogenesis: stepwise assembly?

In vitro studies and structural analyzes have provided a very good understanding of the assembly of the SRP in vitro, as well as of the protein-protein and protein-RNA interactions, and the SRP 3D structure (for reviews, see Refs. [46,47,48,49]). The hetero-dimerization of SRP9 and SRP14 is required for their binding to 7SL RNA [50]. SRP68 and SRP72 are also associated with 7SL RNA as a heterodimer [3,51], but each protein has the capability to bind 7SL RNA independently of the other, at least

Processing and post-transcriptional modification of 7SL RNA

7SL RNA is transcribed by the RNA polymerase III (polIII) and bears a triphosphate 5′ end [70]. The 3′ extremity of human 7SL RNA has the sequence CUCUUU-OH. The last three terminal uridylic residues are post-transcriptionally removed and an adenylic acid residue is added by the poly(A) polymerase γ [71,72]. The polIII termination factor La binds the 7SL RNA through its 3′-oligo(U) tract and is required for its accurate processing, at least in yeast [73]. The 7SL RNA present in the nucleolus is

Trafficking of SRP during its biogenesis

How are SRP proteins imported into the nucleus and how do they reach the nucleolus? How is the 7SL RNA targeted to the nucleolus? How does the pre-SRP leave the nucleolus and is exported to the cytoplasm? All these processes are still unclear and most of the factors required need to be characterized. In yeast, each SRP protein enters the nucleus independently of the other proteins [63,64]. Srp68p, Srp72p, Srp14p and Srp21p are imported by the importins/karyopherins Pse1p and Kap123p [64]. The

Assembly of eukaryotic SRP requires the SMN complex

The SMN complex contains the SMN protein, associated with Gemin2 to 8 and Unrip proteins. This complex is essential for cell survival and is present in all eukaryotes tested so far except in the yeast S. cerevisiae. Reduced levels of the SMN protein lead to a severe pathology, spinal muscular atrophy (SMA), which is an autosomal recessive neuromuscular disease characterized by muscle atrophy and paralysis, mainly due to degeneration and loss of the α motor neurons of the spinal cord anterior

Conclusion

Eukaryotic SRP biogenesis is a stepwise process that takes place at least partially in the nucleolus. Remarkably, apart from the SMN complex and a few other proteins involved in RNA processing and cellular trafficking, no other factor involved in the biogenesis of SRP has been identified to date. How SRP is assembled and how its biogenesis is regulated are far from being understood. Further studies are needed to 1) understand the precise function of the SMN complex in SRP assembly and to look

Conflict of interest

There is no conflict of interest.

Acknowledgements

Many thanks to Dr. S. Labialle for comments on the manuscript. S. Massenet is supported by the French Centre National de la Recherche Scientifique (CNRS), the University of Lorraine and the “Association pour la recherche contre la Sclérose Latérale Amyotrophique » (ARSLA).

References (90)

  • A.E. Sauer-Eriksson et al.

    S-domain assembly of the signal recognition particle

    Curr. Opin. Struct. Biol.

    (2003)
  • E. Iakhiaeva et al.

    Identification of an RNA-binding domain in human SRP72

    J. Mol. Biol.

    (2005)
  • C. Oubridge et al.

    Crystal structure of SRP19 in complex with the S domain of SRP RNA and its implication for the assembly of the signal recognition particle

    Mol. Cell

    (2002)
  • E. Menichelli et al.

    Protein-induced conformational changes of RNA during the assembly of human signal recognition particle

    J. Mol. Biol.

    (2007)
  • R. Reddy

    Characterization and subcellular localization of 7-8 S RNAs of Novikoff hepatoma

    J. Biol. Chem.

    (1981)
  • L.F. Ciufo et al.

    Nuclear export of yeast signal recognition particle lacking Srp54p by the Xpo1p/Crm1p NES-dependent pathway

    Curr. Biol.

    (2000)
  • T.S. Maity et al.

    A threefold RNA-protein interface in the signal recognition particle gates native complex assembly

    J. Mol. Biol.

    (2007)
  • W.Y. Li et al.

    Nucleotide sequence of 7 S RNA. Homology to alu DNA and La 4.5 S RNA

    J. Biol. Chem.

    (1982)
  • K.M. Sinha et al.

    Adenylation of small RNAs in human cells. Development of a cell-free system for accurate adenylation on the 3'-end of human signal recognition particle RNA

    J. Biol. Chem.

    (1998)
  • K. Perumal et al.

    Purification, characterization, and cloning of the cDNA of human signal recognition particle RNA 3'-adenylating enzyme

    J. Biol. Chem.

    (2001)
  • Y. Chen et al.

    Accurate 3' end processing and adenylation of human signal recognition particle RNA and alu RNA in vitro

    J. Biol. Chem.

    (1998)
  • C.N. Alavian et al.

    Nuclear export of signal recognition particle RNA in mammalian cells

    Biochem. Biophys. Res. Commun.

    (2004)
  • S. Lefebvre

    Identification and characterization of a spinal muscular atrophy- determining gene [see comments]

    Cell

    (1995)
  • R.N. Singh et al.

    Diverse role of survival motor neuron protein

    Biochim. Biophys. Acta

    (2017)
  • D.K. Li et al.

    SMN control of RNP assembly: from post-transcriptional gene regulation to motor neuron disease

    Semin. Cell Dev. Biol.

    (2014)
  • P.J. Young

    Nuclear gems and Cajal (coiled) bodies in fetal tissues: nucleolar distribution of the spinal muscular atrophy protein, SMN

    Exp. Cell Res.

    (2001)
  • K.A. Wehner

    Survival motor neuron protein in the nucleolus of mammalian neurons

    Brain Res.

    (2002)
  • P. Traub et al.

    Structure and function of E. coli ribosomes. V. Reconstitution of functionally active 30S ribosomal particles from RNA and proteins

    Proc. Natl. Acad. Sci. U. S. A.

    (1968)
  • K.H. Nierhaus et al.

    Total reconstitution of functionally active 50S ribosomal subunits from Escherichia coli

    Proc. Natl. Acad. Sci. U. S. A.

    (1974)
  • I. Tozik et al.

    Reconstitution of the signal recognition particle of the halophilic archaeon Haloferax volcanii

    Nucleic Acids Res.

    (2002)
  • S.F. Ataide

    The crystal structure of the signal recognition particle in complex with its receptor

    Science

    (2011)
  • J.H. Lee

    Sequential activation of human signal recognition particle by the ribosome and signal sequence drives efficient protein targeting

    Proc. Natl. Acad. Sci. U. S. A.

    (2018)
  • V.A. Raker et al.

    Spliceosomal U snRNP core assembly: Sm proteins assemble onto an Sm site RNA nonanucleotide in a specific and thermodynamically stable manner

    Mol. Cell Biol.

    (1999)
  • V. Segault et al.

    In vitro reconstitution of mammalian U2 and U5 snRNPs active in splicing: Sm proteins are functionally interchangeable and are essential for the formation of functional U2 and U5 snRNPs

    EMBO J.

    (1995)
  • B. Charpentier et al.

    Reconstitution of archaeal H/ACA small ribonucleoprotein complexes active in pseudouridylation

    Nucleic Acids Res.

    (2005)
  • U. Fischer et al.

    Assembly of RNPs: help needed

    RNA

    (2015)
  • D.L. Lafontaine

    Noncoding RNAs in eukaryotic ribosome biogenesis and function

    Nat. Struct. Mol. Biol.

    (2015)
  • E. Cerezo

    Maturation of pre-40S particles in yeast and humans, Wiley interdisciplinary reviews

    RNA

    (2019)
  • J. Bassler et al.

    Eukaryotic ribosome assembly

    Annu. Rev. Biochem.

    (2018)
  • O.J. Gruss et al.

    UsnRNP biogenesis: mechanisms and regulation

    Chromosoma

    (2017)
  • S. Massenet et al.

    Assembly and trafficking of box C/D and H/ACA snoRNPs

    RNA Biol.

    (2017)
  • N. Aviram et al.

    Targeting and translocation of proteins to the endoplasmic reticulum at a glance

    J. Cell Sci.

    (2017)
  • M.R. Pool

    Signal recognition particles in chloroplasts, bacteria, yeast and mammals (review)

    Mol. Membr. Biol.

    (2005)
  • M.A. Rosenblad et al.

    Kinship in the SRP RNA family

    RNA Biol.

    (2009)
  • E.D. Gundelfinger et al.

    The organization of the 7SL RNA in the signal recognition particle

    Nucleic Acids Res.

    (1983)
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