کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
8293804 | 1536748 | 2018 | 7 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Regulation of Tak1 alternative splicing by splice-switching oligonucleotides
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کلمات کلیدی
PTCTGF-β activated kinase 1AONsVivo-morpholinoSplice-switching oligonucleotidesTAK1NMDSPFHFDPSIAntisense oligonucleotides - oligonucleotide antisenseamyotrophic lateral sclerosis - اسکلروز جانبی آمیوتروفیکALS - بیماری اسکلروز جانبی آمیوتروفیکAlternative splicing - جابجایی جایگزینhigh-fat diet - رژیم غذایی با چربی بالاnonsense-mediated mRNA decay - فرسودن mRNA ناشی از بی معنی استLipid metabolism - متابولیسم لیپیدspecific pathogen free - پاتوژن خاص رایگان استpremature termination codon - کدون از بین بردن زودرس
موضوعات مرتبط
علوم زیستی و بیوفناوری
بیوشیمی، ژنتیک و زیست شناسی مولکولی
زیست شیمی
پیش نمایش صفحه اول مقاله
چکیده انگلیسی
Alternative splicing (AS) generates multiple isoforms from a single precursor mRNA, and these isoforms usually exhibit different tissue distributions and functions. Aberrant protein isoforms can lead to abnormalities in protein function and may even result in genetic disorders or cancer. In recent years, splice-switching oligonucleotides (SSOs) have emerged as a promising therapeutic strategy for several neurological diseases, but the efficacy of this strategy in other organs is less reported. In this study, we designed and synthesized SSOs targeting the splicing regulators of exon 12 of the Tak1 gene, inducing variant switching between Tak1-A and Tak1-B. We also designed SSOs capable of knockdown both Tak1 variants by inducing the aberrant splicing of exon 4. The Vivo-morpholino SSOs showed significant splice-switching of Tak1 in mouse liver, with a persistence of at least 10 days after initial SSOs delivery. Bioinformatics analysis indicated a lipid metabolism-related function for Tak1-B but not Tak1-A. The conversion of Tak1-B to Tak1-A consistently led to significant accumulation of lipids in cultured AML12â¯cells, as well as the dysregulation of several lipid metabolism-related genes in mouse liver. Different functional properties of the two isoforms may explain the conflicting functions previously reported for Tak1. In conclusion, our research clarified the different functions of Tak1 isoforms, and provided an efficient strategy for the functional research of the AS isoforms.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Biochemical and Biophysical Research Communications - Volume 497, Issue 4, 18 March 2018, Pages 1018-1024
Journal: Biochemical and Biophysical Research Communications - Volume 497, Issue 4, 18 March 2018, Pages 1018-1024
نویسندگان
Donghu Zhou, Qianqian Shao, Xu Fan, Peng Wu, Weiran Lin, Handong Wei, Fuchu He, Ying Jiang,