Long non-coding RNA CR46040 is essential for injury-stimulated regeneration of intestinal stem cells in Drosophila
Long non-coding RNA CR46040 is essential for injury-stimulated regeneration of intestinal stem cells in Drosophila
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DOI：
10.1093/genetics/iyad040
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发表时间：
2023
期刊：
影响因子：
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通讯作者：
Xiaolin Bi
中科院分区：
文献类型：
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作者：
Qi Xu;Jun Liu;Xiao Du;Di Xue;Dong Li;Xiaolin Bi
Abstract. Long non-coding RNAs (lncRNAs) play important regulatory roles in stem cells self-renewal, pluripotency maintenance and differentiation. Till now, there is very limited knowledge about how lncRNAs regulate intestinal stem cells (ISCs), and lncRNAs mediating ISCs regeneration in Drosophila have yet been characterized. Here, we identify a lncRNA, CR46040, that is essential for the injury-induced ISCs regeneration in Drosophila. Loss of CR46040 greatly impairs ISCs proliferation in response to tissue damage caused by dextran sulfate sodium (DSS) treatment. We demonstrate that CR46040 is a genuine lncRNA that has two isoforms transcribed from the same transcription start site, and works in trans to regulate intestinal stem cells. Mechanistically, CR46040 knock-out flies are failed to fully activate JNK, JAK/STAT and HIPPO signaling pathways after tissue damage, which are required for ISCs proliferation after intestinal injury. Moreover, CR46040 knock-out flies are highly susceptible to DSS treatment and enteropathogenic bacteria Erwinia carotovora ssp. carotovora 15 (Ecc15) infection. Our findings characterize, for the first time, a lncRNA that mediates damage-induced ISCs proliferation in Drosophila, and provide new insights into the functional links among the long non-coding RNAs, ISCs proliferation and tissue homeostasis.
