Xbp1的ligase发现

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这篇笔记聚焦于2014年两篇关键文献,它们共同揭示了哺乳动物未折叠蛋白响应(UPR)中XBP1 mRNA非经典剪接的关键酶——RtcB RNA连接酶的发现。文章对比了不同的筛选策略,并探讨了RtcB的细胞定位及其功能补偿的可能性。

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两篇文章,都是2014年发表,第二篇的筛选更有趣一点:

The mammalian tRNA ligase complex mediates splicing of XBP1 mRNA and controls antibody secretion in plasma cells | The EMBO Journal

A Synthetic Biology Approach Identifies the Mammalian UPR RNA Ligase RtcB: Molecular Cell

第一篇里有RTCB在Hela cell的定位(both nucleus and cytosol)

第二篇文章提到,RTCB对于XBP1的非经典剪接可能还有additional pathway.

In RtcB cKO cells, a small portion of XBP1s was still produced in the absence of RtcB, suggesting that an additional RNA ligase might compensate for RtcB function. Unlike mammalian cells, yeast HAC1 mRNA splicing is mediated by the 5′-PO4/3′-OH ligation pathway utilizing tRNA ligase Trl1p and 2′-phosphotransferase Tpt1p (Gonzalez et al., 1999; Schwer et al., 2004; Sidrauski et al., 1996). Consistent with this observation, a similar RNA ligase activity has been detected biochemically in HeLa cell extract, but the identity of such ligase remains unknown (Zillmann et al., 1991). Therefore, it is possible that an RNA ligase in the 5′-PO4/3′-OH pathway compensates for loss of RtcB ligase activity in RtcB-null cells. Nevertheless, we have shown that the cells expressing ligase-dead RtcB exhibited a nearly complete loss of XBP1s protein and XBP1s mRNA, suggesting that RtcBC122A may act as a dominant-negative protein to prevent XBP1u substrates from being ligated by a compensatory RNA ligase.

有话这里说 ↓