小柯机器人

美国马萨诸塞大学陈医学院Katherine A. Fitzgerald和Liraz Shmuel-Galia共同合作，近期取得重要工作进展。他们研究发现，lncRNA HOXA11os调节骨髓细胞的线粒体功能以维持肠道稳态。相关研究成果2023年7月25日在线发表于《细胞—代谢》杂志上。

据介绍，这项研究揭示了一种以前未被表征的机制，通过从非编码基因组基因座转录的调节RNA来限制肠道炎症。

研究人员鉴定了一种在远端结肠中特异性表达的lncRNA HOXA11os的新转录物，该转录物在结肠炎中降低到检测不到的水平。HOXA11os在基础条件下定位于线粒体，并与电子传输链（ETC）复合物1的核心亚基相互作用以维持其活性。结肠髓细胞中HOXA11os的缺乏导致复合体I缺乏、功能失调的氧化磷酸化（OXPHOS）和线粒体活性氧（mtROS）的产生。因此，HOXA11os缺陷小鼠会发生自发的肠道炎症，并对结肠炎过敏。

总之，这一研究确定了一个新的调节轴，lncRNA通过调节复合体I的活性来维持肠道稳态并限制结肠炎症。

附：英文原文

Title: The lncRNA HOXA11os regulates mitochondrial function in myeloid cells to maintain intestinal homeostasis

Author: Liraz Shmuel-Galia, Fiachra Humphries, Tim Vierbuchen, Zhaozhao Jiang, Nolan Santos, John Johnson, Boris Shklyar, Leonel Joannas, Nicholas Mustone, Shany Sherman, Doyle Ward, JeanMarie Houghton, Christina E. Baer, Aisling O’Hara, Jorge Henao-Mejia, Kasper Hoebe, Katherine A. Fitzgerald

Issue&Volume: 2023-07-25

Abstract: This study reveals a previously uncharacterized mechanism to restrict intestinal inflammationvia a regulatory RNA transcribed from a noncoding genomic locus. We identified a noveltranscript of the lncRNA HOXA11os specifically expressed in the distal colon thatis reduced to undetectable levels in colitis. HOXA11os is localized to mitochondriaunder basal conditions and interacts with a core subunit of complex 1 of the electrontransport chain (ETC) to maintain its activity. Deficiency of HOXA11os in colonicmyeloid cells results in complex I deficiency, dysfunctional oxidative phosphorylation(OXPHOS), and the production of mitochondrial reactive oxygen species (mtROS). Asa result, HOXA11os-deficient mice develop spontaneous intestinal inflammation andare hypersusceptible to colitis. Collectively, these studies identify a new regulatoryaxis whereby a lncRNA maintains intestinal homeostasis and restricts inflammationin the colon through the regulation of complex I activity.

DOI: 10.1016/j.cmet.2023.06.019

Source: https://www.cell.com/cell-metabolism/fulltext/S1550-4131(23)00250-4

Cell Metabolism：《细胞—代谢》，创刊于2005年。隶属于细胞出版社，最新IF：31.373
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