Mini-reviewIn vivo assembly of eukaryotic signal recognition particle: A still enigmatic process involving the SMN complex
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).
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