Sequestration of RBM10 in Nuclear Bodies: Targeting Sequences and Biological Significance

International Journal of Molecular Sciences

Naoki Yamamoto¹  Koji Nishio²  Tokio Tani³  Kazuaki Tokunaga³  Hong Zhao⁴  Koichi Nakajima⁴  Akira Inoue⁴  Hirotada Kojima⁴  Hiroyuki Kunimoto⁴  Ling-Yu Wang⁴  Sheng-Jun Xiao⁴  Kishiko Sunami⁵  Takahiro Yamamoto⁶  Masatsugu Kimura⁷ 

[1] Center for Basic Medical Research, and Graduate School of Pharmaceutical Sciences, International University of Health and Welfare, Ohtawara 324-8501, Japan;Department of Anatomy and Neurosciences, Graduate School of Medicine, Nagoya University, Nagoya 466-8550, Japan;Department of Biological Sciences, Graduate School of Science and Technology, Kumamoto University, Kumamoto 860-8555, Japan;Department of Immunology, Graduate School of Medicine, Osaka City University, Osaka 545-8585, Japan;Department of Otolaryngology, Graduate School of Medicine, Osaka City University, Osaka 545-8585, Japan;Graduate School of Life Science, Hokkaido University, Sapporo 060-0808, Japan;Radioisotope Center, Graduate School of Medicine, Osaka City University, Osaka 545-8585, Japan;

关键词: RBM10;    S1-1 nuclear body;    nuclear body-targeting sequence;    C₂H₂ Zn finger;    alternative splicing;    transcription;   

DOI  :  10.3390/ijms221910526

来源: DOAJ

【 摘 要 】

RBM10 is an RNA-binding protein that regulates alternative splicing (AS). It localizes to the extra-nucleolar nucleoplasm and S1-1 nuclear bodies (NBs) in the nucleus. We investigated the biological significance of this localization in relation to its molecular function. Our analyses, employing deletion mutants, revealed that RBM10 possesses two S1-1 NB-targeting sequences (NBTSs), one in the KEKE motif region and another in the C₂H₂ Zn finger (ZnF). These NBTSs act synergistically to localize RBM10 to S1-1 NBs. The C₂H₂ ZnF not only acts as an NBTS, but is also essential for AS regulation by RBM10. Moreover, RBM10 does not participate in S1-1 NB formation, and without alterations of RBM10 protein levels, its NB-localization changes, increasing as cellular transcriptional activity declines, and vice versa. These results indicate that RBM10 is a transient component of S1-1 NBs and is sequestered in NBs via its NBTSs when cellular transcription decreases. We propose that the C₂H₂ ZnF exerts its NB-targeting activity when RBM10 is unbound by pre-mRNAs, and that NB-localization of RBM10 is a mechanism to control its AS activity in the nucleus.

【 授权许可】

Unknown