کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
8840567 | 1614690 | 2018 | 42 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Impaired Local Translation of β-actin mRNA in Ighmbp2-Deficient Motoneurons: Implications for Spinal Muscular Atrophy with respiratory Distress (SMARD1)
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کلمات کلیدی
RNAseqSMARD1IGHMBP2FPKMmotoneuronHelicaseFRAPROIHEPES4-(2-hydroxyethyl)-1-piperazineethanesulfonic acid - 4- (2-hydroxyethyl) -1-piperazineethanesulfonic acidEDTA - اتیلن دی آمین تترا استیک اسید Ethylenediaminetetraacetic acid - اتیلینیدامین تتراستیک اسیدRNA immunoprecipitation - ایمن سازی RNARNA sequencing - ترتیب RNATranslation - ترجمه (زیستشناسی)fluorescence recovery after photobleaching - فلوئورسانس پس از فوتوبلاسیکfluorescence in situ hybridization - فلورسانس در هیبریداسیون در محلFish - ماهیregion of interest - منطقه مورد نظرRIP - پاره کردن
موضوعات مرتبط
علوم زیستی و بیوفناوری
علم عصب شناسی
علوم اعصاب (عمومی)
پیش نمایش صفحه اول مقاله
چکیده انگلیسی
Spinal muscular atrophy with respiratory distress type 1 (SMARD1) is a fatal motoneuron disorder in children with unknown etiology. The disease is caused by mutations in the IGHMBP2 gene, encoding a Super Family 1 (SF1)-type RNA/DNA helicase. IGHMBP2 is a cytosolic protein that binds to ribosomes and polysomes, suggesting a role in mRNA metabolism. Here we performed morphological and functional analyses of isolated immunoglobulin μ-binding protein 2 (Ighmbp2)-deficient motoneurons to address the question whether the SMARD1 phenotype results from de-regulation of protein biosynthesis. Ighmbp2-deficient motoneurons exhibited only moderate morphological aberrations such as a slight increase of axonal branches. Consistent with the rather mild phenotypic aberrations, RNA sequencing of Ighmbp2-deficient motoneurons revealed only minor transcriptome alterations compared to controls. Likewise, we did not detect any global changes in protein synthesis using pulsed SILAC (Stable Isotope Labeling by Amino acids in Cell culture), FUNCAT (FlUorescent Non-Canonical Amino acid Tagging) and SUnSET (SUrface SEnsing of Translation) approaches. However, we observed reduced β-actin protein levels at the growth cone of Ighmbp2-deficient motoneurons which was accompanied by reduced level of IMP1/ZBP1, a known interactor of β-actin mRNA. Fluorescence Recovery after Photobleaching (FRAP) studies revealed translational down-regulation of an eGFP-myr-β-actin 3â²UTR mRNA in growth cones. Local translational regulation of β-actin mRNA was dependent on the 3â² UTR but independent of direct Ighmbp2-binding to β-actin mRNA. Taken together, our data indicate that Ighmbp2 deficiency results in local but modest disruption of protein biosynthesis which might partially contribute to the motoneuron defects seen in SMARD1.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Neuroscience - Volume 386, 21 August 2018, Pages 24-40
Journal: Neuroscience - Volume 386, 21 August 2018, Pages 24-40
نویسندگان
Verena Surrey, Caren Zöller, Alicia Andrea Lork, Mehri Moradi, Stefanie Balk, Benjamin Dombert, Lena Saal-Bauernschubert, Michael Briese, Silke Appenzeller, Utz Fischer, Sibylle Jablonka,