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现在位置:首页 > 科研进展 > 最新重要论文(影响因子PNAS及以上)
A Circular RNA Protects Dormant Hematopoietic Stem Cells from DNA Sensor cGAS-Mediated Exhaustion, Immunity, 48(4):p688–701, 17 April 2018
2018-05-07 | 【     】【打印】【关闭

Immunity, 48(4):p688–701.e7, 17 April 2018,DOI: 10.1016/j.immuni.2018.03.016

A Circular RNA Protects Dormant Hematopoietic Stem Cells from DNA Sensor cGAS-Mediated Exhaustion

Pengyan Xia, Shuo Wang, Buqing Ye, Ying Du, Chong Li, Zhen Xiong, Yuan Qu, Zusen Fan

Abstract

Disrupting the balance between self-renewal and differentiation of hematopoietic stem cells (HSCs) leads to bone marrow failure or hematologic malignancy. However, how HSCs sustain their quiescent state and avoid type I interferon (IFN)-mediated exhaustion remains elusive. Here we defined a circular RNA that we named cia-cGAS that was highly expressed in the nucleus of long-term (LT)-HSCs. Cia-cGAS deficiency in mice caused elevated expression of type I IFNs in bone marrow and led to decreased numbers of dormant LT-HSCs. Under homeostatic conditions, cia-cGAS bound DNA sensor cGAS in the nucleus to block its synthase activity, thereby protecting dormant LT-HSCs from cGAS-mediated exhaustion. Moreover, cia-cGAS harbored a stronger binding affinity to cGAS than self-DNA did and consequently suppressed cGAS-mediated production of type I IFNs in LT-HSCs. Our findings reveal a mechanism by which cia-cGAS inhibits nuclear cGAS by blocking its enzymatic activity and preventing cGAS from recognizing self-DNA to maintain host homeostasis.

文章链接:https://www.cell.com/immunity/fulltext/S1074-7613(18)30092-X

 

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