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TERC promotes cellular inflammatory response independent of telomerase

Liu, Haiying, Yang, Yiding, Ge, Yuanlong, Liu, Juanhong, Zhao, Yong·2019·Nucleic Acids Research
DOI 10.1093/nar/gkz584PMC PMC6735767
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Abstract

TERC is an RNA component of telomerase. However, TERC is also ubiquitously expressed in most human terminally differentiated cells, which don’t have telomerase activity. The function of TERC in these cells is largely unknown. Here, we report that TERC enhances the expression and secretion of inflammatory cytokines by stimulating NK-κB pathway in a telomerase-independent manner. The ectopic expression of TERC in telomerase-negative cells alters the expression of 431 genes with high enrichment of those involved in cellular immunity. We perform genome-wide screening using a previously identified ‘binding motif’ of TERC and identify 14 genes that are transcriptionally regulated by TERC. Among them, four genes (LIN37, TPRG1L, TYROBP and USP16) are demonstrated to stimulate the activation of NK-κB pathway. Mechanistically, TERC associates with the promoter of these genes through forming RNA–DNA triplexes, thereby enhancing their transcription. In vivo, expression levels of TERC and TERC target genes (TYROBP, TPRG1L and USP16) are upregulated in patients with inflammation-related diseases such as type II diabetes and multiple sclerosis. Collectively, these results reveal an unknown function of TERC on stimulating inflammatory response and highlight a new mechanism by which TERC modulates gene transcription. TERC may be a new target for the development of anti-inflammation therapeutics.

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  • Terc is specific to cells of hematopoietic origin.

    “our data suggest that Terc is specific to cells of hematopoietic origin.”

    From A mouse tissue atlas of small noncoding RNA (2020) · cites this paper as [40]

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Sorted by citations

Authors
Liu, H., Yang, Y., Ge, Y., Liu, J., & Zhao, Y.
Affiliations
  • MOE Key Laboratory of Gene Function and Regulation, School of Life Sciences, Sun Yat-sen University, Guangzhou 510006, P.R. China
  • Department of Endocrinology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, P.R. China
Venue
Nucleic Acids Research
Publisher
Oxford University Press (OUP)
Published
2019-07-11
Volume
47
Issue
15
Pages
8084-8095
ISSN
  • 0305-1048
  • 1362-4962
DOI
10.1093/nar/gkz584
PMC
PMC6735767
Cited by
77
References
3
Language
en
Licence
creativecommons.org/licenses/by/4.0/ (vor)
Funders
  • National Natural Science Foundation of China (81771506, 31571410)
  • National Key R&D Program of China (2018YFA0107000)
  • Guangzhou Municipal People's Livelihood Science and Technology Plan (201803010108)

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