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Roles for Srp72p in assembly, nuclear export and function of the signal recognition particle

Lookup NU author(s): Dr Robert Van Nues, Eileen Leung, Iswarya Dantuluru, Dr Jeremy Brown

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Abstract

Co-translational protein targeting to the endoplasmic reticulum is catalysed by the signal recognition particle, a conserved ribonucleoprotein. Key activities of SRP - signal sequence binding, and inhibition of ribosomal translation elongation - require interactions of SRP with distant locations on the ribosome. A heterodimer of Srp72p and Srp68p localise to the central portion of the SRP complex, and may co-ordinate its activities. A series of mutations within Srp72p were examined individually, in combination and in the presence of mutations within SRP RNA. In this analysis mutations within Srp72p fell into two groups, identifying separate interactions/functions of the protein. Much of Srp72p is predicted to be alpha helical tetratricopeptide repeat motifs, with the C-terminus forming a separate unstructured region. Mutations towards the C-terminal end of the alpha helical region reveal a specific genetic interaction with a conserved motif in the central helix of SRP RNA. In contrast, mutations within the C-terminal region of Srp72p have genetic interactions across the RNA. Many mutant combinations impaired function rather than inhibiting assembly of SRP. However, one specific combination of Srp72p and SRP RNA mutations led to accumulation of pre-SRP in the nucleus. We conclude that Srp72p has at least two functions that are individually redundant and that the conformation of the complex is critical for efficient completion of its biogenesis. ©2008 Landes Bioscience.


Publication metadata

Author(s): van Nues RW, Leung E, McDonald J, Dantuluru I, Brown JD

Publication type: Article

Publication status: Published

Journal: RNA Biology

Year: 2008

Volume: 5

Issue: 2

Pages: 73-83

ISSN (print): 1547-6286

ISSN (electronic): 1555-8584

Publisher: Landes Bioscience

URL: http://dx.doi.org/10.4161/rna.5.2.6042

DOI: 10.4161/rna.5.2.6042


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Funding

Funder referenceFunder name
Wellcome Trust
BB/D008816/1Biotechnology and Biological Sciences Research Council
G117/395Medical Research Council

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