Shao Tzu-Ling, Ting Ruei-Teng, Lee Ming-Chia
Department of Life Sciences and Institute of Genome Sciences, National Yang Ming Chiao Tung University, Taipei, Taiwan.
Department of Life Sciences and Institute of Genome Sciences, National Yang Ming Chiao Tung University, Taipei, Taiwan.
Cell Rep. 2022 Aug 30;40(9):111294. doi: 10.1016/j.celrep.2022.111294.
Lysine-specific demethylase 1 (Lsd1) plays a key role in balancing cell proliferation and differentiation. Lsd1 has been recently reported to associate with specific long noncoding RNAs (lncRNAs) to account for oncogenic gene expression in cancer cells. However, how lncRNA-Lsd1 interplay affects cell-specific differentiation remains elusive in vivo. Here, through Lsd1 specific RNA immunopecipitation sequencing (RIP-seq) experiments, we identify three long hairpin RNAs as Lsd1-interacting non-coding RNAs (LINRs) from fly ovaries. Knocking out LINR-1 and LINR-2 affects fly egg production, while each of the LINR deletion mutant females produce eggs with reduced hatch rate, indicating important functions of LINRs in supporting oogenesis. At the cellular level, LINR-2 regulates the differentiation of germline stem cells and follicle progenitors likely though modulating the expression and function of Lsd1 in vivo. Our identification of ovarian LINRs presents a physiological example of dynamic lncRNA-Lsd1 interplay that regulates stem cell/progenitor differentiation.
赖氨酸特异性去甲基化酶1（Lsd1）在平衡细胞增殖和分化中起关键作用。最近有报道称，Lsd1与特定的长链非编码RNA（lncRNA）相关联，从而导致癌细胞中致癌基因的表达。然而，在体内，lncRNA-Lsd1相互作用如何影响细胞特异性分化仍不清楚。在这里，通过Lsd1特异性RNA免疫沉淀测序（RIP-seq）实验，我们从果蝇卵巢中鉴定出三种长发夹RNA作为与Lsd1相互作用的非编码RNA（LINR）。敲除LINR-1和LINR-2会影响果蝇产卵，而每个LINR缺失突变体雌性产生的卵孵化率降低，这表明LINR在支持卵子发生中具有重要功能。在细胞水平上，LINR-2可能通过调节体内Lsd1的表达和功能来调节生殖系干细胞和卵泡祖细胞的分化。我们对卵巢LINR的鉴定提供了一个动态lncRNA-Lsd1相互作用调节干细胞/祖细胞分化的生理学实例。
