Open AccessMir‐23a induces telomere dysfunction and cellular senescence by inhibiting TRF 2 expression
Author(s) -
Luo Zhenhua,
Feng Xuyang,
Wang Haoli,
Xu Weiyi,
Zhao Yong,
Ma Wenbin,
Jiang Songshan,
Liu Dan,
Huang Junjiu,
Songyang Zhou
Publication year - 2015
Publication title -
aging cell
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.103
H-Index - 140
eISSN - 1474-9726
pISSN - 1474-9718
DOI - 10.1111/acel.12304
Subject(s) - telomere , senescence , biology , microrna , microbiology and biotechnology , endogeny , untranslated region , three prime untranslated region , downregulation and upregulation , messenger rna , genetics , gene , biochemistry
Summary Telomeric repeat binding factor 2 ( TRF 2) is essential for telomere maintenance and has been implicated in DNA damage response and aging. Telomere dysfunction induced by TRF 2 inhibition can accelerate cellular senescence in human fibroblasts. While previous work has demonstrated that a variety of factors can regulate TRF 2 expression transcriptionally and post‐translationally, whether micro RNA s (mi RNA s) also participate in post‐transcriptionally modulating TRF 2 levels remains largely unknown. To better understand the regulatory pathways that control TRF 2, we carried out a large‐scale luciferase reporter screen using a mi RNA expression library and identified four mi RNA s that could target human TRF 2 and significantly reduce the level of endogenous TRF 2 proteins. In particular, our data revealed that miR‐23a could directly target the 3′ untranslated region (3′ UTR ) of TRF 2. Overexpression of miR‐23a not only reduced telomere‐bound TRF 2 and increased telomere dysfunction‐induced foci ( TIF s), but also accelerated senescence of human fibroblast cells, which could be rescued by ectopically expressed TRF 2. Our findings demonstrate that TRF 2 is a specific target of miR‐23a, and uncover a previously unknown role for miR‐23a in telomere regulation and cellular senescence.