Anantharaman Aparna, Gholamalamdari Omid, Khan Abid, Yoon Je-Hyun, Jantsch Michael F, Hartner Jochen C, Gorospe Myriam, Prasanth Supriya G, Prasanth Kannanganattu V
Department of Cell and Developmental Biology, University of Illinois at Urbana-Champaign, IL, USA.
Laboratory of Genetics and Genomics, National Institute of Aging-Intramural Research Program, NIH, Baltimore, MD, USA.
FEBS Lett. 2017 Sep;591(18):2890-2904. doi: 10.1002/1873-3468.12795. Epub 2017 Aug 30.
Adenosine deaminases acting on RNA (ADARs) are proteins that catalyse widespread A-to-I editing within RNA sequences. We recently reported that ADAR2 edits and stabilizes nuclear-retained Cat2 transcribed nuclear RNA (Ctn RNA). Here, we report that ADAR1 coordinates with ADAR2 to regulate editing and stability of Ctn RNA. We observe an RNA-dependent interaction between ADAR1 and ADAR2. Furthermore, ADAR1 negatively regulates interaction of Ctn RNA with RNA-destabilizing proteins. We also show that breast cancer (BC) cells display elevated ADAR1 but not ADAR2 levels, compared to nontumourigenic cells. Additionally, BC patients with elevated levels of ADAR1 show low survival. Our findings provide insights into overlapping substrate preferences of ADARs and potential involvement of ADAR1 in BC.
作用于RNA的腺苷脱氨酶（ADARs）是一类能催化RNA序列中广泛的A到I编辑的蛋白质。我们最近报道，ADAR2对核内保留的Cat2转录核RNA（Ctn RNA）进行编辑并使其稳定。在此，我们报道ADAR1与ADAR2协同作用以调节Ctn RNA的编辑和稳定性。我们观察到ADAR1与ADAR2之间存在RNA依赖性相互作用。此外，ADAR1负向调节Ctn RNA与RNA不稳定蛋白之间的相互作用。我们还表明，与非致瘤细胞相比，乳腺癌（BC）细胞中ADAR1水平升高，但ADAR2水平未升高。此外，ADAR1水平升高的BC患者生存率较低。我们的研究结果为深入了解ADARs重叠的底物偏好以及ADAR1在BC中的潜在作用提供了见解。
