کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
8300453 | 1537275 | 2015 | 38 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
From transcriptomic to protein level changes in TDP-43 and FUS loss-of-function cell models
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کلمات کلیدی
HTSS.I.Exon arrayFTDf.c.TDP-43FUs - FUSRBPs - RBP هاamyotrophic lateral sclerosis - اسکلروز جانبی آمیوتروفیکALS - بیماری اسکلروز جانبی آمیوتروفیکfold change - تغییر در برابرKEGG یا Kyoto Encyclopedia of Genes and Genomes - دایرة المعارف ژن ها و ژنوم کیوتو Kyoto Encyclopedia of Genes and Genomes - دایره المعارف ژنتیک ژن ها و ژنوم کیوتوhigh-throughput screening - غربالگری بالاfrontotemporal dementia - فراموشی پیشانی گیجگاهی، انحطاط پیشانی گیجگاهیGene ontology - هستیشناسی ژنیWestern blot - وسترن بلاتRNA-binding protein - پروتئین متصل به RNARNA-binding proteins - پروتئین های مرتبط با RNASplicing - چسباندن
موضوعات مرتبط
علوم زیستی و بیوفناوری
بیوشیمی، ژنتیک و زیست شناسی مولکولی
زیست شیمی
پیش نمایش صفحه اول مقاله
![عکس صفحه اول مقاله: From transcriptomic to protein level changes in TDP-43 and FUS loss-of-function cell models From transcriptomic to protein level changes in TDP-43 and FUS loss-of-function cell models](/preview/png/8300453.png)
چکیده انگلیسی
The full definition of the physiological RNA targets regulated by TDP-43 and FUS RNA-binding proteins (RBPs) represents an important issue in understanding the pathogenic mechanisms associated to these two proteins in amyotrophic lateral sclerosis and frontotemporal dementia. In the last few years several high-throughput screenings have generated a plethora of data, which are difficult to compare due to the different experimental designs and models explored. In this study by using the Affymetrix Exon Arrays, we were able to assess and compare the effects of both TDP-43 and FUS loss-of-function on the whole transcriptome using the same human neuronal SK-N-BE cell model. We showed that TDP-43 and FUS depletion induces splicing and gene expression changes mainly distinct for the two RBPs, although they may regulate common pathways, including neuron differentiation and cytoskeleton organization as evidenced by functional annotation analysis. In particular, TDP-43 and FUS were found to regulate splicing and expression of genes related to neuronal (SEPT6, SULT4A1, TNIK) and RNA metabolism (DICER, ELAVL3/HuC, POLDIP3). Our extended analysis at protein level revealed that these changes have also impact on the protein isoform ratio and content, not always in a direct correlation with transcriptomic data. Contrarily to a loss-of-function mechanism, we showed that mutant TDP-43 proteins maintained their splicing activity in human ALS fibroblasts and experimental cell lines. Our findings further contribute to define the biological functions of these two RBPs in physiological and disease state, strongly encouraging the evaluation of the identified transcriptomic changes at protein level in neuronal experimental models.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Biochimica et Biophysica Acta (BBA) - Gene Regulatory Mechanisms - Volume 1849, Issue 12, December 2015, Pages 1398-1410
Journal: Biochimica et Biophysica Acta (BBA) - Gene Regulatory Mechanisms - Volume 1849, Issue 12, December 2015, Pages 1398-1410
نویسندگان
Claudia Colombrita, Elisa Onesto, Emanuele Buratti, Pierre de la Grange, Valentina Gumina, Francisco E. Baralle, Vincenzo Silani, Antonia Ratti,