URH49 exports mRNA by remodeling complex formation and mediating the NXF1-dependent pathway

Publication date: Available online 7 January 2020Source: Biochimica et Biophysica Acta (BBA) - Gene Regulatory MechanismsAuthor(s): Ken-ichi Fujita, Tomohiro Yamazaki, Kotaro Harada, Shigeto Seno, Hideo Matsuda, Seiji MasudaAbstractThe TREX complex integrates information from nuclear mRNA processing events to ensure the timely export of mRNA to the cytoplasm. In humans, UAP56 and its paralog URH49 form distinct complexes, the TREX complex and the AREX complex, respectively, which cooperatively regulate the expression of a specific set of mRNA species on a genome wide scale. The difference in the complex formation between UAP56 and URH49 are thought to play a critical role in the regulation of target mRNAs. To date, the underlying mechanism remains poorly understood. Here we characterize the formation of the TREX complex and the AREX complex. In the ATP depleted condition, UAP56 formed an Apo-TREX complex containing the THO subcomplex but not ALYREF and CIP29. URH49 formed an Apo-AREX complex containing CIP29 but not ALYREF and the THO subcomplex. However, with the addition of ATP, both the Apo-TREX complex and the Apo-AREX complex were remodeled to highly similar ATP-TREX complex containing the THO subcomplex, ALYREF and CIP29. The knockdown of URH49 caused a reduction in its target mRNAs and a cytokinesis failure. Similarly, cytokinesis abnormality was observed in CIP29 knockdown cells, suggesting that CIP29 belongs to the URH49 regulated mRNA export pathway. Lastly, we conf...

Source: Biochimica et Biophysica Acta (BBA) Gene Regulatory Mechanisms - January 8, 2020 Category: Genetics & Stem Cells Source Type: research