The Association of the Human PM/Scl-75 Autoantigen with the Exosome Is Dependent on a Newly Identified N Terminus

Raijmakers, Reinout; Egberts, Wilma Vree; Venrooij, Walther J. van; Pruijn, Ger J. M.

doi:10.1074/jbc.m302488200

Cited by 25 publications

(24 citation statements)

References 25 publications

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“…The distribution of the exosome complex has been confirmed in these cellular locations, with the highest concentration reported in the nucleoli (Raijmakers et al, 2003(Raijmakers et al, , 2004. This is not the case with the CER7 protein in Arabidopsis.…”

Section: Discussionsupporting

confidence: 53%

A Core Subunit of the RNA-Processing/Degrading Exosome Specifically Influences Cuticular Wax Biosynthesis inArabidopsis

et al. 2007

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The cuticle is an extracellular matrix composed of cutin polyester and waxes that covers aerial organs of land plants and protects them from environmental stresses. The Arabidopsis thaliana cer7 mutant exhibits reduced cuticular wax accumulation and contains considerably lower transcript levels of ECERIFERUM3/WAX2/YORE-YORE (CER3/WAX2/YRE), a key wax biosynthetic gene. We show here that CER7 protein is a putative 39-59 exoribonuclease homologous to yeast Ribonuclease PH45 (RRP45p), a core subunit of the RNA processing and degrading exosome that controls the expression of CER3/ WAX2/YRE. We propose that CER7 acts by degrading a specific mRNA species encoding a negative regulator of CER3/ WAX2/YRE transcription. A second RRP45p homolog found in Arabidopsis, designated At RRP45a, is partially functionally redundant with CER7, and complete loss of RRP45 function in Arabidopsis is lethal. To our knowledge, CER7 is currently the only example of a core exosomal subunit specifically influencing a cellular process. INTRODUCTIONThe epidermal cells of primary organs of all land plants are covered with a cuticle, a continuous lipid layer that limits nonstomatal water loss, prevents organ fusion during development (Lolle et al., 1998;Sieber et al., 2000), and protects plants against numerous biotic and abiotic environmental factors, including bacterial and fungal pathogens, temperature extremes, and UV light. The cuticle is composed of cutin, an insoluble polyester of C16 and C18 hydroxy and epoxy fatty acids and glycerol (Graç a et al., 2002;Nawrath, 2002) that is surrounded and covered with waxes, predominantly aliphatic derivatives of very long chain fatty acids easily extracted with organic solvents (Kunst and Samuels, 2003).In recent years, genetic studies have yielded some insights into wax biosynthetic pathways (Kunst et al., 2006) and uncovered a transporter that can move wax constituents across the plasma membrane (Pighin et al., 2004). However, little is known about the regulation of cuticular wax deposition, an issue of fundamental importance for the development of plant cultivars with improved cuticle properties that are more resistant to environmental stresses. Currently, the only regulatory proteins known to affect wax production are the WAX INDUCER1/SHINE family in Arabidopsis thaliana and WAX PRODUCTION ACTIVA-TOR1 in Medicago truncatula (Aharoni et al., 2004;Broun et al., 2004;Zhang et al., 2005). Overexpression of these APETALA2/ ETHYLENE RESPONSE FACTOR-type transcription factors dramatically enhances wax accumulation in leaves of transgenic plants, but their in planta roles in regulating wax deposition have not yet been confirmed by analysis of loss-of-function mutants.To identify mutants defective in regulation of wax production, we examined the expression of the cloned wax biosynthetic genes in all the wax-deficient eceriferum (cer) lines of Arabidopsis described by Koornneef et al. (1989). The cer7 mutant was found to have reduced transcript levels of CER3/WAX2/YORE-YORE (YRE) (CER3 is allelic to WAX2/...

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Section: Discussionsupporting

confidence: 53%

A Core Subunit of the RNA-Processing/Degrading Exosome Specifically Influences Cuticular Wax Biosynthesis inArabidopsis

et al. 2007

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“…Previous studies have shown that human exosome subunits are localized both in the nucleus and particularly enriched in the nucleolus and in the cytoplasm (37,38). However, it was not reported that cytoplasmic exosome subunits are localized to discrete granules.…”

Section: Amd Requires Function Of Parn-mentioning

confidence: 92%

“…However, it was not reported that cytoplasmic exosome subunits are localized to discrete granules. Because the nuclear/nucleolar staining of exosome subunits is usually stronger than that of cytoplasmic signals (37,38), the appearance of cytoplasmic exosome granules might have been overlooked. Our finding of human exosome subunits concentrated in cytoplasmic granules is consistent with a recent study suggesting that several Drosophila exosome subunits are enriched in cytoplasmic foci (40).…”

Section: Amd Requires Function Of Parn-mentioning

confidence: 99%

Localization of AU-rich Element-containing mRNA in Cytoplasmic Granules Containing Exosome Subunits

Lin

Duffy

Chen

2007

Journal of Biological Chemistry

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Eukaryotic mRNAs can be degraded in either decapping/5-to-3 or 3-to-5 direction after deadenylation. In yeast and mammalian cells, decay factors involved in the 5-to-3 decay pathway are concentrated in cytoplasmic processing bodies (P bodies). The mechanistic steps and localization of mammalian mRNA decay are still not completely understood. Here, we investigate functions of human mRNA decay enzymes in AU-rich element (ARE)-mediated mRNA decay (AMD) and find that the deadenylase, poly(A) ribonuclease PARN, and enzymes involved in the 5-to-3 and 3-to-5 decay pathways are required for AMD. The ARE-containing reporter mRNA accumulates in discrete cytoplasmic granular structures, which are distinct from P bodies and stress granules. These granules consist of poly(A)-specific ribonuclease, exosome subunits, and decay-promoting ARE-binding proteins. Inhibition of AMD increases accumulation of ARE-mRNA in these granules. We refer to these structures as cytoplasmic exosome granules and suggest that some AMD may occur in these granules.

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“…The full-length PM-Scl-75 open reading frame was amplified from PM-Scl-75c construct (Raijmakers et al 2003) using the primers 59-CCGAGCCTGCAGATGAAGGAAAC GCCACTCTCA and 59-GACCGGTACCTTAATTGGCAGCTCTC CTCTT. Select domains of the protein were amplified from the plasmid as follows: Primers to amplify the C-terminal amino acids 351-439 were 59-AATAAACTGCAGAGACTCTGAGAAGGAAG ATGATGAA and 59-AATGCTTCGAATTCCCATATGGTAC; primers to amplify the C-terminal amino acids 285-439 were 59-AATAAACTGCAGAGAGTCTATAGCAAATCAAAGGATC and 59-AAGCTTCGAATTCCCATATGGTAC.…”

Section: Methodsmentioning

confidence: 99%

Sequence-specific RNA binding mediated by the RNase PH domain of components of the exosome

Anderson¹,

Mukherjee²,

Muthukumaraswamy³

et al. 2006

RNA

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We have previously demonstrated that PM-Scl-75, a component of the human exosome complex involved in RNA maturation and mRNA decay, can specifically interact with RNAs containing an AU-rich instability element. Through the analysis of a series of deletion mutants, we have now shown that a 266 amino acid fragment representing the RNase PH domain is responsible for the sequence-specific binding to AU-rich elements. Furthermore, we found that the RNase PH domains from two other exosomal components, OIP2 and RRP41, as well as from Escherichia coli polynucleotide phosphorylase, are all capable of specifically interacting with RNAs containing an AU-rich element with similar affinities. Finally, we demonstrate that the interaction of the RNase PH domain of PM-Scl-75 is readily competed by poly(U), but only inefficiently using other homopolymeric RNAs. These data demonstrate that RNase PH domains in general have an affinity for U-and AU-rich sequences, and broaden the potential role in RNA biology of proteins containing these domains.

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The Association of the Human PM/Scl-75 Autoantigen with the Exosome Is Dependent on a Newly Identified N Terminus

Cited by 25 publications

References 25 publications

A Core Subunit of the RNA-Processing/Degrading Exosome Specifically Influences Cuticular Wax Biosynthesis inArabidopsis

A Core Subunit of the RNA-Processing/Degrading Exosome Specifically Influences Cuticular Wax Biosynthesis inArabidopsis

Localization of AU-rich Element-containing mRNA in Cytoplasmic Granules Containing Exosome Subunits

Sequence-specific RNA binding mediated by the RNase PH domain of components of the exosome

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