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SLIRP stabilizes LRPPRC via an RRM-PPR protein interface

Lookup NU author(s): Dr Agata Rozanska, Professor Robert Lightowlers, Professor Zofia Chrzanowska-Lightowlers

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This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License (CC BY-NC 4.0).


Abstract

LRPPRC is a protein that has attracted interest both for its role in post-transcriptional regulation of mitochondrial gene expression and more recently because numerous mutated variants have been characterized as causing severe infantile mitochondrial neurodegeneration. LRPPRC belongs to the pentatricopeptide repeat (PPR) protein family, originally defined by their RNA binding capacity, and forms a complex with SLIRP that harbours an RNA recognition motif (RRM) domain. We show here that LRPPRC displays a broad and strong RNA binding capacity in vitro in contrast to SLIRP that associates only weakly with RNA. The LRPPRC-SLIRP complex comprises a hetero-dimer via interactions by polar amino acids in the single RRM domain of SLIRP and three neighbouring PPR motifs in the second quarter of LRPPRC, which critically contribute to the LRPPRC-SLIRP binding interface to enhance its stability. Unexpectedly, specific amino acids at this interface are located within the PPRs of LRPPRC at positions predicted to interact with RNA and within the RNP1 motif of SLIRP's RRM domain. Our findings thus unexpectedly establish that despite the prediction that these residues in LRPPRC and SLIRP should bind RNA, they are instead used to facilitate protein-protein interactions, enabling the formation of a stable complex between these two proteins.


Publication metadata

Author(s): Spahr H, Rozanska A, Li XP, Atanassov I, Lightowlers RN, Chrzanowska-Lightowlers ZMA, Rackham O, Larsson NG

Publication type: Article

Publication status: Published

Journal: Nucleic Acids Research

Year: 2016

Volume: 44

Issue: 14

Pages: 6868-6882

Print publication date: 19/08/2016

Online publication date: 28/06/2016

Acceptance date: 16/06/2016

Date deposited: 26/10/2016

ISSN (print): 0305-1048

ISSN (electronic): 1362-4962

Publisher: Oxford University Press

URL: http://dx.doi.org/10.1093/nar/gkw575

DOI: 10.1093/nar/gkw575


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