کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
11022626 | 1701476 | 2019 | 9 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
A natural “GA” insertion mutation in the sequence encoding the 3â²UTR of CXCL12/SDF-1α: Identification, characterization, and functional impact on mRNA splicing
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کلمات کلیدی
CXCRSDFPhytohemagglutininPBLPTCARMSRIPAdNTPCXCLAREsdeoxyriboC-X-C chemokine receptorChemokine CXCL12G-quadruplexesC-X-C motif chemokine ligandTrans-activator of transcriptionPBSFUTRPBSORFPBMCCPMPHAcDNA - cDNADMSO - DMSODNA complementary to RNA - DNA مکمل RNAMTI - MTamino acid(s) - آمینو اسیدهاTAT - تاتamplification refractory mutation system - تقویت سیستم جهش مقاومتیBase pair(s) - جفت پایه (ها)mutation - جهشMutant - جهش یافتهdeletion - حذفdeoxyribonucleoside triphosphate - دز اکسید ریبونوکلئوزید تری فسفاتDimethyl sulfoxide - دیمتیل سولفواکسیدTranscription - رونویسیreverse transcription - رونویسی معکوسperipheral blood mononuclear cells - سلول های تک هسته ای خون محیطیcounts per minute - شمار در هر دقیقهStromal cell derived factor - عامل استخراج سلول استروماAU-rich elements - عناصر غنی AUphosphate buffer saline - فسفات بافر شورopen reading frame - قاب خواندن بازperipheral blood lymphocytes - لنفوسیت های خون محیطیuntranslated region(s) - ناحیه (های) غیر مترادفwild type - نوع وحشیpolymerase chain reaction - واکنش زنجیره ای پلیمرازPCR - واکنش زنجیرهٔ پلیمرازhuman immunodeficiency virus - ویروس نقص ایمنی انسانیHIV - ویروس نقص ایمنی انسانی premature termination codon - کدون از بین بردن زودرس
موضوعات مرتبط
علوم زیستی و بیوفناوری
بیوشیمی، ژنتیک و زیست شناسی مولکولی
ژنتیک
پیش نمایش صفحه اول مقاله
چکیده انگلیسی
The CXCL12 gene produces a series of transcript variants through alternative splicing at the 3â² end of its pre-mRNA. This study explores the biological activities of these alternative transcripts and the mechanisms involved in the regulation of CXCL12 transcription and RNA splicing. We identified a “GA” insertion mutation in the region of CXCL12α DNA encoding the conserved 3â²UTR. This variant transcript was named CXCL12-3â²GA+. The mutation occurred at a frequency of 13.2% in healthy Chinese individuals. However, its frequency in healthy Caucasians was 22.6%, significantly higher than what was observed in the Chinese. Genomic analysis indicated that the GA+ mutation likely encodes a G-quadruplex structure in close proximity to a cluster of important AU-rich elements (AREs) that are well-established regulators of mRNA stability at the 3â²UTR. Experiments using molecular constructs encoding the 3â²UTR of CXCL12 revealed that the GA+ allele can significantly increase gene expression compared to the WT allele. Further studies uncovered that the WT allele was associated with the production of a 225-bp minor transcript isoform (MTI) through alternative splicing resulting in the deletion of exon 2. ARMS-PCR using samples collected from cultured PBMCs of WT/GA+ genotype carriers indicated that the GA+ allele was preferentially transcribed compared to the WT allele. In summary, the study demonstrates that a GA insertion in the region encoding the 3â²UTR of CXCL12α may affect gene expression through alternative mRNA splicing. This finding provides a basis for understanding how multiple elements in the sequence encoding the 3â²UTR of the CXCL12 gene regulates its transcription and may lead to insights about diseases involving abnormal CXCL12α expression.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Gene - Volume 681, 10 January 2019, Pages 36-44
Journal: Gene - Volume 681, 10 January 2019, Pages 36-44
نویسندگان
Xiuying Zhao, Dong Zhu, Haojie Zhang, Hongyan Sui, Vincent Poon, Shibo Jiang, Bojian Zheng,