RT Journal Article SR Electronic T1 Targeting of RBM10 to S1-1 Nuclear Bodies: Targeting Sequences and its Biological Significance JF bioRxiv FD Cold Spring Harbor Laboratory SP 516831 DO 10.1101/516831 A1 Ling-Yu Wang A1 Sheng-Jun Xiao A1 Hiroyuki Kunimoto A1 Kazuaki Tokunaga A1 Hirotada Kojima A1 Masatsugu Kimura A1 Takahiro Yamamoto A1 Naoki Yamamoto A1 Zhao Hong A1 Koji Nishio A1 Hideo Yamane A1 Tokio Tani A1 Koichi Nakajima A1 Hiroyoshi Iguchi A1 Akira Inoue YR 2019 UL http://biorxiv.org/content/early/2019/01/10/516831.abstract AB RBM10 is an RNA-binding protein that regulates alternative splicing (AS). This protein localizes to the extra-nucleolar nucleoplasm and S1-1 nuclear bodies (NBs). We investigated the biological significance of RBM10 localization to S1-1 NBs, which is poorly understood. Our analyses 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 acted synergistically and were sufficient for localization of RBM10 to S1-1 NBs. Furthermore, the C2H2 ZnF not only acted as an NBTS, but was also essential for regulation of AS by RBM10. RBM10 did not participate in S1-1 NB formation. We confirmed the previous finding that localization of RBM10 to S1-1 NBs increases as cellular transcriptional activity decreases and vice versa. These results indicate that RBM10 is a transient component of S1-1 NBs and is sequestered in these structures via its NBTSs when cellular transcription decreases. We propose that the NB-targeting activity of the C2H2 ZnF is induced when it is not bound to pre-mRNA or the splicing machinery complex under conditions of reduced transcription.