Alternative polyadenylation drives genome-to-phenome information detours in the AMPKα1 and AMPKα2 knockout mice
| العنوان: | Alternative polyadenylation drives genome-to-phenome information detours in the AMPKα1 and AMPKα2 knockout mice |
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| المؤلفون: | Jon F. Davis, Jennifer J. Michal, Guoli Ji, Yangzi Zhang, Zhihua Jiang, Xing Fu, Xiang Zhou, Shuwen Zhang, Min Du |
| المصدر: | Scientific Reports Scientific Reports, Vol 8, Iss 1, Pp 1-10 (2018) |
| بيانات النشر: | Springer Science and Business Media LLC, 2018. |
| سنة النشر: | 2018 |
| مصطلحات موضوعية: | 0301 basic medicine, Myosin light-chain kinase, Genotype, Polyadenylation, lcsh:Medicine, AMP-Activated Protein Kinases, Biology, Muscle Development, Article, Mice, 03 medical and health sciences, Nebulin, Animals, lcsh:Science, Muscle, Skeletal, Gene knockout, Mice, Knockout, Genome, Multidisciplinary, Myogenesis, lcsh:R, Adenosine Monophosphate, Cell biology, Mice, Inbred C57BL, Phenotype, 030104 developmental biology, PFKM, Knockout mouse, biology.protein, lcsh:Q, Transcriptome, Carbonic anhydrase 3 |
| الوصف: | Currently available mouse knockout (KO) lines remain largely uncharacterized for genome-to-phenome (G2P) information flows. Here we test our hypothesis that altered myogenesis seen in AMPKα1- and AMPKα2-KO mice is caused by use of alternative polyadenylation sites (APSs). AMPKα1 and AMPKα2 are two α subunits of adenosine monophosphate-activated protein kinase (AMPK), which serves as a cellular sensor in regulation of many biological events. A total of 56,483 APSs were derived from gastrocnemius muscles. The differentially expressed APSs (DE-APSs) that were down-regulated tended to be distal. The DE-APSs that were related to reduced and increased muscle mass were down-regulated in AMPKα1-KO mice, but up-regulated in AMPKα2-KO mice, respectively. Five genes: Car3 (carbonic anhydrase 3), Mylk4 (myosin light chain kinase family, member 4), Neb (nebulin), Obscn (obscurin) and Pfkm (phosphofructokinase, muscle) utilized different APSs with potentially antagonistic effects on muscle function. Overall, gene knockout triggers genome plasticity via use of APSs, completing the G2P processes. However, gene-based analysis failed to reach such a resolution. Therefore, we propose that alternative transcripts are minimal functional units in genomes and the traditional central dogma concept should be now examined under a systems biology approach. |
| تدمد: | 2045-2322 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::29ebafd4e2c34a96aa5bc2d8beb0ada5Test https://doi.org/10.1038/s41598-018-24683-7Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....29ebafd4e2c34a96aa5bc2d8beb0ada5 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 20452322 |
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