Correction: Short GCG expansions in the PABP2 gene cause oculopharyngeal muscular dystrophy

Brais, Bernard; Al., Et

doi:10.1038/1304

Cited by 21 publications

(25 citation statements)

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“…The protein has an N-terminus rich in glutamate residues, followed by an RNP-type RNA binding domain and an argininerich C-terminus [74]. PABP2 has recently received some attention because mutations leading to oculopharyngeal muscular dystrophy have been mapped to the PABP2 gene [75]. The protein carries at its N-terminus the sequence Met-Ala 10 -Gly-Ala 2 .…”

Section: Cleavage and Polyadenylation Factorsmentioning

confidence: 99%

3′-End processing of pre-mRNA in eukaryotes

Wahle¹

1999

FEMS Microbiology Reviews

180

236

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Abstract3P-Ends of almost all eukaryotic mRNAs are generated by endonucleolytic cleavage and addition of a poly(A) tail. In mammalian cells, the reaction depends on the sequence AAUAAA upstream of the cleavage site, a degenerate GU-rich sequence element downstream of the cleavage site and stimulatory sequences upstream of AAUAAA. Six factors have been identified that carry out the two reactions. With a single exception, they have been purified to homogeneity and cDNAs for 11 subunits have been cloned. Some of the cooperative RNA-protein and protein-protein interactions within the processing complex have been analyzed, but many details, including the identity of the endonuclease, remain unknown. Several examples of regulated polyadenylation are being analyzed at the molecular level. In the yeast Saccharomyces cerevisiae, sequences directing cleavage and polyadenylation are more degenerate than in metazoans, and a downstream element has not been identified. The list of processing factors may be complete now with approximately a dozen polypeptides, but their functions in the reaction are largely unknown. 3P-Processing is known to be coupled to transcription. This connection is thought to involve interactions of processing factors with the mRNA cap as well as with RNA polymerase II. ß

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Section: Cleavage and Polyadenylation Factorsmentioning

confidence: 99%

3′-End processing of pre-mRNA in eukaryotes

Wahle¹

1999

FEMS Microbiology Reviews

180

236

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“…Codon expansions in the gene for the human nuclear poly(A) binding protein PABPN1 result in the extension of a natural oligoalanine stretch of 10 residues positioned directly after the start methionine to a maximum of 17 alanines. Individuals possessing this extension develop the disease oculopharyngeal muscular dystrophy, 1 which is histochemically characterized by amyloid-like intranuclear inclusions, containing PABPN1 as the major constituent. 2 The seven Ala extension of the protein leads to an enhanced propensity to fibrillize, as shown for the N-terminal domain of PABPN1, abbreviated N-(+7)Ala. 3 The fibrils are characterized by extreme robustness similar to spider silk, which also contain oligoalanine stretches.…”

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confidence: 99%

Structural and Dynamical Characterization of Fibrils from a Disease-Associated Alanine Expansion Domain Using Proteolysis and Solid-State NMR Spectroscopy

et al. 2008

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The nuclear poly(A) binding protein PABPN1 possesses a natural 10 alanine stretch that can be extended to 17 Ala by codon expansion. The expansions are associated with the disease oculopharyngeal muscular dystrophy (OPMD), which is characterized histopathologically by intranuclear fibrillar deposits. Here, we have studied the Ala extended fibrillar N-terminal fragment of PABPN1, (N-(+7)Ala), comprising 152 amino acids. At natural abundance, cross-polarized 13C MAS NMR spectra are dominated by the three Ala signals with characteristic beta-sheet chemical shifts. In contrast, directly polarized 13C MAS spectra show a multitude of narrow lines, suggesting a large portion of highly mobile sites. Proteolytic cleavage of the protein combined with MALDI-TOF mass spectrometry revealed a protease-resistant peptide encompassing residues 13/14 to 50-52 with the poly-Ala stretch in the center. Measurements of the 1H-13Calpha dipolar couplings of 13C/15N-labeled N-(+7)Ala revealed high order parameters of 0.77 for the poly-Ala stretch of the fibril, while the majority of the residues of N-(+7)Ala exhibited very low order parameters between 0.06 and 0.15. Only some Gly residues that are flanking the Ala-rich region had significant order parameters of 0.47. Thus, site-specific dynamic mapping represents a useful tool to identify the topology of fibrillar proteins.

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“…Many individuals with OPMD from North America and Europe carry a mutant (GCG) 9 or (GCN) 13 allele. [3] Studies from the UK showed an equal distribution of (GCG) 9 and (GCG) 10 (or (GCN) 13 and (GCN) 14 ) mutations, [10] and in Hispanic New Mexicans, the (GCG) 9 mutation was also commonly identified. [11] Our SA Afrikaner family has the (GCG) 11 (GCA) 3 GCG (or (GCN) 15 ) mutation, which has been established to be a founder mutation in Uruguayan and Mexican families.…”

Section: Discussionmentioning

confidence: 99%

A South African family with oculopharyngeal muscular dystrophy: Clinical and molecular genetic characteristics

et al. 2015

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Autosomal dominantly inherited oculopharyngeal muscular dystrophy (OPMD) is caused by a trinucleotide repeat expansion in exon 1 of the polyadenylate binding protein nuclear 1 (PABPN1) gene on chromosome 14q. A large family with OPMD was recently identified in Pretoria, South Africa (SA). Molecular studies revealed a (GCG)11(GCA)3GCG or (GCN)15 mutant allele. The (GCN)15 mutation detected in this family has been described previously in families from Uruguay and Mexico as a founder effect. To our knowledge, this is the first report of an SA Afrikaner family with molecularly confirmed OPMD. The proband, a 64-year-old woman, presented to the neurology outpatient department at Steve Biko Academic Hospital, Pretoria. A sibship of 18 individuals was identified, of whom eight had OPMD. Four patients were interviewed and examined clinically, and electromyographic studies were performed. Molecular analysis of the PABPN1 gene was performed by polymerase chain reaction amplification and direct sequencing of exon 1 in three of the patients. Patients presented with ptosis, external ophthalmoplegia, dysphagia, dysarthria and mild proximal weakness. High foot arches and absent ankle reflexes raised the possibility of peripheral neuropathy, but electromyography showed only mildly low sensory amplitudes, and myopathic units in two patients.

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Correction: Short GCG expansions in the PABP2 gene cause oculopharyngeal muscular dystrophy

Cited by 21 publications

References 0 publications

3′-End processing of pre-mRNA in eukaryotes

3′-End processing of pre-mRNA in eukaryotes

Structural and Dynamical Characterization of Fibrils from a Disease-Associated Alanine Expansion Domain Using Proteolysis and Solid-State NMR Spectroscopy

A South African family with oculopharyngeal muscular dystrophy: Clinical and molecular genetic characteristics

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