Szewczyk Maciej, Fedoryszak-Kuśka Natalia, Tkaczuk Katarzyna, Dobrucki Jurek, Waligórska Agnieszka, Stępień Piotr P
Institute of Genetics and Biotechnology, Faculty of Biology, Warsaw University, Warsaw, Poland.
Centre for New Technologies, University of Warsaw, Warsaw, Poland.
Acta Biochim Pol. 2017;64(1):177-181. doi: 10.18388/abp.2016_1419. Epub 2017 Mar 15.
The human SUV3 helicase (SUV3, hSUV3, SUPV3L1) is a DNA/RNA unwinding enzyme belonging to the class of DexH-box helicases. It localizes predominantly in the mitochondria, where it forms an RNA-degrading complex called mitochondrial degradosome with exonuclease PNP (polynucleotide phosphorylase). Association of this complex with the polyA polymerase can modulate mitochondrial polyA tails. Silencing of the SUV3 gene was shown to inhibit the cell cycle and to induce apoptosis in human cell lines. However, since small amounts of the SUV3 helicase were found in the cell nuclei, it was not clear whether the observed phenotypes of SUV3 depletion were of mitochondrial or nuclear origin. In order to answer this question we have designed gene constructs able to inhibit the SUV3 activity exclusively in the cell nuclei. The results indicate that the observed growth rate impairment upon SUV3 depletion is due to its nuclear function(s). Unexpectedly, overexpression of the nuclear-targeted wild-type copies of the SUV3 gene resulted in a higher growth rate. In addition, we demonstrate that the SUV3 helicase can be found in the HeLa cell nucleoli, but it is not detectable in the DNA-repair foci. Our results indicate that the nucleolar-associated human SUV3 protein is an important factor in regulation of the cell cycle.
人类SUV3解旋酶（SUV3、hSUV3、SUPV3L1）是一种DNA/RNA解旋酶，属于DexH盒解旋酶家族。它主要定位于线粒体，在那里它与核酸外切酶PNP（多核苷酸磷酸化酶）形成一种名为线粒体降解体的RNA降解复合物。该复合物与聚腺苷酸聚合酶的结合可调节线粒体聚腺苷酸尾巴。研究表明，SUV3基因沉默可抑制人类细胞系的细胞周期并诱导细胞凋亡。然而，由于在细胞核中发现了少量的SUV3解旋酶，因此尚不清楚观察到的SUV3缺失表型是源于线粒体还是细胞核。为了回答这个问题，我们设计了能够仅在细胞核中抑制SUV3活性的基因构建体。结果表明，SUV3缺失后观察到的生长速率受损是由于其核功能。出乎意料的是，SUV3基因的核靶向野生型拷贝的过表达导致更高的生长速率。此外，我们证明SUV3解旋酶可以在HeLa细胞核仁中发现，但在DNA修复位点中无法检测到。我们的结果表明，与核仁相关的人类SUV3蛋白是细胞周期调控中的一个重要因素。
