Structural differences between the closely related RNA helicases, UAP56 and URH49, fashion distinct functional apo-complexes

Ken-ichi Fujita (), Misa Ito, Midori Irie, Kotaro Harada, Naoko Fujiwara, Yuya Ikeda, Hanae Yoshioka, Tomohiro Yamazaki, Masaki Kojima, Bunzo Mikami, Akila Mayeda and Seiji Masuda ()
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Ken-ichi Fujita: Kyoto University, Kyoto
Misa Ito: Kyoto University, Kyoto
Midori Irie: Kyoto University, Kyoto
Kotaro Harada: Kyoto University, Kyoto
Naoko Fujiwara: Kyoto University, Kyoto
Yuya Ikeda: Kyoto University, Kyoto
Hanae Yoshioka: Kyoto University, Kyoto
Tomohiro Yamazaki: Kyoto University, Kyoto
Masaki Kojima: Tokyo University of Pharmacy and Life Sciences
Bunzo Mikami: Kyoto University
Akila Mayeda: Fujita Health University
Seiji Masuda: Kyoto University, Kyoto

Nature Communications, 2024, vol. 15, issue 1, 1-16

Abstract: Abstract mRNA export is an essential pathway for the regulation of gene expression. In humans, closely related RNA helicases, UAP56 and URH49, shape selective mRNA export pathways through the formation of distinct complexes, known as apo-TREX and apo-AREX complexes, and their subsequent remodeling into similar ATP-bound complexes. Therefore, defining the unidentified components of the apo-AREX complex and elucidating the molecular mechanisms underlying the formation of distinct apo-complexes is key to understanding their functional divergence. In this study, we identify additional apo-AREX components physically and functionally associated with URH49. Furthermore, by comparing the structures of UAP56 and URH49 and performing an integrated analysis of their chimeric mutants, we exhibit unique structural features that would contribute to the formation of their respective complexes. This study provides insights into the specific structural and functional diversification of these two helicases that diverged from the common ancestral gene Sub2.

Date: 2024
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DOI: 10.1038/s41467-023-44217-8

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