title: MCPIP1 down-regulates IL-2 expression through an ARE-independent pathway.
abstract: IL-2 plays a key role in the survival and proliferation of immune cells, especially T lymphocytes. Its expression is precisely regulated at transcriptional and posttranscriptional level. IL-2 is known to be regulated by RNA binding proteins, such as tristetraprolin (TTP), via an AU-rich element (ARE) in the 3'-untranslated region (3'UTR) to influence the stability of mRNA. MCPIP1, identified as a novel RNase, can degrade IL-6, IL-12 and TNF-α mRNA by an ARE-independent pathway in the activation of macrophages. Here, we reported that MCPIP1 was induced in the activation of T lymphocytes and negatively regulated IL-2 gene expression in both mouse and human primary T lymphocytes through destabilizing its mRNA. A set of Luciferase reporter assay demonstrated that a non-ARE conserved element in IL-2 3'UTR, which formed a stem-loop structure, responded to MCPIP1 activity.RNA immunoprecipitation and Biotin pulldown experiments further suggested that MCPIP1 could modestly bind to IL-2 mRNA. Taken together, these data demonstrate that MCPIP1 down-regulates IL-2 via an ARE-independent pathway.
authors.affiliation: Institute of Immunology, Zhejiang University School of Medicine, Hangzhou, China.
authors.forename: Min
authors.initials: M
authors.lastname: Li
authors.forename: Wenqiang
authors.initials: W
authors.lastname: Cao
authors.forename: Haifeng
authors.initials: H
authors.lastname: Liu
authors.forename: Wei
authors.initials: W
authors.lastname: Zhang
authors.forename: Xia
authors.initials: X
authors.lastname: Liu
authors.forename: Zhijian
authors.initials: Z
authors.lastname: Cai
authors.forename: Jing
authors.initials: J
authors.lastname: Guo
authors.forename: Xuelian
authors.initials: X
authors.lastname: Wang
authors.forename: Zhaoyuan
authors.initials: Z
authors.lastname: Hui
authors.forename: Hang
authors.initials: H
authors.lastname: Zhang
authors.forename: Jianli
authors.initials: J
authors.lastname: Wang
authors.forename: Lie
authors.initials: L
authors.lastname: Wang
mesh_terms: D020413:3' Untranslated Regions / Q000235:genetics; D063307:AU Rich Elements / Q000235:genetics*; D000818:Animals; D002460:Cell Line; D005786:Gene Expression Regulation; D006801:Humans; D018664:Interleukin-12 / Q000378:metabolism; D007376:Interleukin-2 / Q000235:genetics / Q000378:metabolism; D015850:Interleukin-6 / Q000235:genetics / Q000378:metabolism; D051379:Mice; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D016601:RNA-Binding Proteins / Q000235:genetics; D012260:Ribonucleases; D013601:T-Lymphocytes / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D051816:Tristetraprolin / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D020413:3' Untranslated Regions; D007376:Interleukin-2; D015850:Interleukin-6; D012333:RNA, Messenger; D016601:RNA-Binding Proteins; D014157:Transcription Factors; D051816:Tristetraprolin; D014409:Tumor Necrosis Factor-alpha; D018664:Interleukin-12; D012260:Ribonucleases; C510646:ZC3H12A protein, human