Department of Basic Medical Sciences, Section of Medical Biochemistry, University of Bari Aldo Moro, Bari, Italy.
Biochimie. 2012 Dec;94(12):2600-7. doi: 10.1016/j.biochi.2012.07.022. Epub 2012 Aug 7.
In this study the impact of hUPF1 and hUPF2 knockdown on alternative splicing (AS) isoforms of different genes encoding subunits of respiratory chain complex I and complex IV is described. As expected, loss of both hUPF1 and hUPF2 led to impairment of nonsense-mediated mRNA decay (NMD) and accumulation of PTC-containing NMD substrates generated by both complex I and complex IV genes. The levels of some complex I splice variants, which did not contain PTC as well as the level of some complex I canonical transcripts were, however, affected only by hUPF1 knockdown. This finding confirms that NMD plays a role in the maintenance of the transcriptome integrity and reveals a specific impact of hUPF1 on the regulation of complex I genes.
在这项研究中，描述了 hUPF1 和 hUPF2 敲低对编码呼吸链复合物 I 和复合物 IV 亚基的不同基因的可变剪接 (AS) 异构体的影响。正如预期的那样，hUPF1 和 hUPF2 的缺失均导致无义介导的 mRNA 降解 (NMD) 的损伤以及由复合物 I 和复合物 IV 基因产生的含有 PTC 的 NMD 底物的积累。然而，一些不含有 PTC 的复合物 I 剪接变体的水平以及一些复合物 I 规范转录本的水平仅受到 hUPF1 敲低的影响。这一发现证实了 NMD 在维持转录组完整性方面的作用，并揭示了 hUPF1 对复合物 I 基因调控的特定影响。
