SUMOylation- and GAR1-Dependent Regulation of Dyskerin Nuclear and Subnuclear Localization
- 1 April 2021
- journal article
- research article
- Published by Taylor & Francis Ltd in Molecular and Cellular Biology
- Vol. 41 (4)
- https://doi.org/10.1128/mcb.00464-20
Abstract
The nuclear and subnuclear compartmentalization of the telomerase-associated protein and H/ACA ribonucleoprotein component dyskerin is an important though incompletely understood aspect of H/ACA ribonucleoprotein function. Four SUMOylation sites were previously identified in the C-terminal Nuclear/Nucleolar Localization Signal (N/NoLS) of dyskerin. We found that a cytoplasmic localized C-terminal truncation variant of dyskerin lacking most of the C-terminal N/NoLS represents an under-SUMOylated variant of dyskerin compared to wildtype dyskerin. We demonstrate that mimicking constitutive SUMOylation of dyskerin using a SUMO3-fusion construct can drive nuclear accumulation of this variant, and that the SUMO site K467 in this N/NoLS is particularly important for the subnuclear localization of dyskerin to the nucleolus in a mature H/ACA complex assembly- and SUMO-dependent manner. We also characterize a novel SUMO-interacting motif in the mature H/ACA complex component GAR1 that mediates the interaction between dyskerin and GAR1. Mislocalization of dyskerin, either in the cytoplasm or excluded from the nucleolus, disrupts dyskerin function and leads to reduced interaction of dyskerin with the telomerase RNA. These data indicate a role for dyskerin C-terminal N/NoLS SUMOylation in regulating the nuclear and subnuclear localization of dyskerin, which is essential for dyskerin function as both a telomerase-associated protein and as an H/ACA ribonucleoprotein.Keywords
Funding Information
- Gouvernement du Canada | Canadian Institutes of Health Research (PJT-166130)
This publication has 98 references indexed in Scilit:
- A global S. cerevisiae small ubiquitin‐related modifier (SUMO) system interactomeMolecular Systems Biology, 2013
- Structure of the Shq1-Cbf5-Nop10-Gar1 complex and implications for H/ACA RNP biogenesis and dyskeratosis congenitaThe EMBO Journal, 2011
- CRM1 controls the composition of nucleoplasmic pre-snoRNA complexes to licence them for nucleolar transportThe EMBO Journal, 2011
- Active liquid-like behavior of nucleoli determines their size and shape in Xenopus laevis oocytesProceedings of the National Academy of Sciences of the United States of America, 2011
- The SUMO system controls nucleolar partitioning of a novel mammalian ribosome biogenesis complexThe EMBO Journal, 2011
- A Proteomic Screen for Nucleolar SUMO Targets Shows SUMOylation Modulates the Function of Nop5/Nop58Molecular Cell, 2010
- Proteomics Analysis of Nucleolar SUMO-1 Target Proteins upon Proteasome InhibitionMolecular & Cellular Proteomics, 2009
- Nucleolar protein B23/nucleophosmin regulates the vertebrate SUMO pathway through SENP3 and SENP5 proteasesThe Journal of cell biology, 2008
- The nucleolar SUMO‐specific protease SENP3 reverses SUMO modification of nucleophosmin and is required for rRNA processingEMBO Reports, 2008
- Stepwise RNP assembly at the site of H/ACA RNA transcription in human cellsThe Journal of cell biology, 2006