کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
8260847 | 1534669 | 2013 | 7 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Genome wide array analysis indicates that an amyotrophic lateral sclerosis mutation of FUS causes an early increase of CAMK2N2 in vitro
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کلمات کلیدی
موضوعات مرتبط
علوم زیستی و بیوفناوری
بیوشیمی، ژنتیک و زیست شناسی مولکولی
سالمندی
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چکیده انگلیسی
Mutations in the RNA binding protein FUS (fused in sarcoma) have been linked to a subset of familial amyotrophic lateral sclerosis (ALS) cases. The mutations are clustered in the C-terminal nuclear localization sequence (NLS). Various FUS mutants accumulate in the cytoplasm whereas wild-type (WT) FUS is mainly nuclear. Here we investigate the effect of one ALS causing mutant (FUS-ÎNLS, also known as R495X) on pre-mRNA splicing and RNA expression using genome wide exon-junction arrays. Using a non-neuronal stable cell line with inducible FUS expression, we detected early changes in RNA composition. In particular, mutant FUS-ÎNLS increased calcium/calmodulin-dependent protein kinase II inhibitor 2 (CAMK2N2) at both mRNA and protein levels, whereas WT-FUS had no effect. Chromatin immunoprecipitation experiments showed that FUS-ÎNLS accumulated at the CAMK2N2 promoter region, whereas promoter occupation by WT-FUS remained constant. Given the loss of FUS-ÎNLS in the nucleus through the mutation-induced translocation, this increase of promoter occupancy is surprising. It indicates that, despite the obvious cytoplasmic accumulation, FUS-ÎNLS can act through a nuclear gain of function mechanism.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease - Volume 1832, Issue 8, August 2013, Pages 1129-1135
Journal: Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease - Volume 1832, Issue 8, August 2013, Pages 1129-1135
نویسندگان
Paolo Convertini, Jiayu Zhang, Pierre de la Grange, Lawrence J. Hayward, Haining Zhu, Stefan Stamm,