کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
8259726 | 1534644 | 2015 | 11 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
scaRNAs regulate splicing and vertebrate heart development
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کلمات کلیدی
FDRsnRNAsribosomal RNAsSmall nuclear RNAsrRNAsSHFsmall nucleolar RNAsSnoRNAsRPKMIngenuity Pathways AnalysisRMAncRNACHDqRT-PCRMOSTOFLNARetinitis pigmentosaIPAhpfSMNCHDs - CHD هاnoncoding RNA - RNA غیر Codingquantitative RT-PCR - RT-PCR کمیPulmonary atresia with intact ventricular septum - آترزی ریوی با جداره بطنی مصنوعیspinal muscular atrophy - آتروفی عضلانی نخاعیTruncus arteriosus - آرتروس تناسلیSpliceosome - اسپلیسئوزومLocked Nucleic Acid - اسید نوکلئیک قفل شدهright ventricle - بطن راستCongenital heart disease - بیماری قلبی مادرزادیTetralogy of Fallot - تترالوژی فالوتAlternative splicing - جابجایی جایگزینSMA - دبیرستانSurvival of motor neuron - زنده ماندن از نورون موتورhours post fertilization - ساعت پس از لقاحscaRNA - لاغرSecond heart field - میدان دوم قلبfalse discovery rate - میزان کشف کاذبCongenital heart defects - نقص مادرزادی قلبCongenital heart defect - نقص مادرزادی قلبSplicing - چسباندنZebrafish - گورخرماهی
موضوعات مرتبط
علوم زیستی و بیوفناوری
بیوشیمی، ژنتیک و زیست شناسی مولکولی
سالمندی
پیش نمایش صفحه اول مقاله
چکیده انگلیسی
Alternative splicing (AS) plays an important role in regulating mammalian heart development, but a link between misregulated splicing and congenital heart defects (CHDs) has not been shown. We reported that more than 50% of genes associated with heart development were alternatively spliced in the right ventricle (RV) of infants with tetralogy of Fallot (TOF). Moreover, there was a significant decrease in the level of 12 small cajal body-specific RNAs (scaRNAs) that direct the biochemical modification of specific nucleotides in spliceosomal RNAs. We sought to determine if scaRNA levels influence patterns of AS and heart development. We used primary cells derived from the RV of infants with TOF to show a direct link between scaRNA levels and splice isoforms of several genes that regulate heart development (e.g., GATA4, NOTCH2, DAAM1, DICER1, MBNL1 and MBNL2). In addition, we used antisense morpholinos to knock down the expression of two scaRNAs (scarna1 and snord94) in zebrafish and saw a corresponding disruption of heart development with an accompanying alteration in splice isoforms of cardiac regulatory genes. Based on these combined results, we hypothesize that scaRNA modification of spliceosomal RNAs assists in fine tuning the spliceosome for dynamic selection of mRNA splice isoforms. Our results are consistent with disruption of splicing patterns during early embryonic development leading to insufficient communication between the first and second heart fields, resulting in conotruncal misalignment and TOF. Our findings represent a new paradigm for determining the mechanisms underlying congenital cardiac malformations.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease - Volume 1852, Issue 8, August 2015, Pages 1619-1629
Journal: Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease - Volume 1852, Issue 8, August 2015, Pages 1619-1629
نویسندگان
Prakash Patil, Nataliya Kibiryeva, Tamayo Uechi, Jennifer Marshall, James E. Jr., Michael Artman, Naoya Kenmochi, Douglas C. Bittel,