title: Interleukin-17 (IL-17) and IL-1 activate translation of overlapping sets of mRNAs, including that of the negative regulator of inflammation, MCPIP1.
abstract: Changes in gene expression during inflammation are in part caused by post-transcriptional mechanisms. A transcriptome-wide screen for changes in ribosome occupancy indicated that the inflammatory cytokine IL-17 activates translation of a group of mRNAs that overlaps partially with those affected similarly by IL-1. Included are mRNAs of IκBζ and of MCPIP1, important regulators of the quality and course of immune and inflammatory responses. Evidence for increased ribosome association of these mRNAs was also obtained in LPS-activated RAW264.7 macrophages and human peripheral blood mononuclear cells. Like IL-1, IL-17 activated translation of IκBζ mRNA by counteracting the function of a translational silencing element in its 3'-UTR defined previously. Translational silencing of MCPIP1 mRNA in unstimulated cells resulted from the combined suppressive activities of its 5'-UTR, which contains upstream open reading frames, and of its 3'-UTR, which silences independently of the 5'-UTR. Only the silencing function of the 3'-UTR was counteracted by IL-17 as well as by IL-1. Translational silencing by the 3'-UTR was dependent on a putative stem-loop-forming region previously associated with rapid degradation of the mRNA. The results suggest that translational control exerted by IL-1 and IL-17 plays an important role in the coordination of an inflammatory reaction.
authors: Institute of Biochemistry, Hannover Medical School, D-30623 Hannover, Germany.
authors: Sonam
authors: S
authors: Dhamija
authors: Reinhard
authors: R
authors: Winzen
authors: Anneke
authors: A
authors: Doerrie
authors: Gesine
authors: G
authors: Behrens
authors: Nancy
authors: N
authors: Kuehne
authors: Celina
authors: C
authors: Schauerte
authors: Elena
authors: E
authors: Neumann
authors: Oliver
authors: O
authors: Dittrich-Breiholz
authors: Michael
authors: M
authors: Kracht
authors: Helmut
authors: H
authors: Holtmann
mesh_terms: D020413:3' Untranslated Regions; D020121:5' Untranslated Regions; D000818:Animals; D002460:Cell Line; D016207:Cytokines / Q000378:metabolism; D005786:Gene Expression Regulation; D020868:Gene Silencing; D006367:HeLa Cells; D006801:Humans; D007249:Inflammation; D007375:Interleukin-1 / Q000378:metabolism*; D020381:Interleukin-17 / Q000378:metabolism*; D051379:Mice; D020411:Oligonucleotide Array Sequence Analysis; D014176:Protein Biosynthesis; D012333:RNA, Messenger / Q000378:metabolism*; D012260:Ribonucleases / Q000378:metabolism*; D014157:Transcription Factors / Q000378:metabolism*; D015533:Transcriptional Activation
chemical_list: D020413:3' Untranslated Regions; D020121:5' Untranslated Regions; D016207:Cytokines; D007375:Interleukin-1; D020381:Interleukin-17; D012333:RNA, Messenger; D014157:Transcription Factors; D012260:Ribonucleases; C510646:ZC3H12A protein, human; C541320:Zc3h12a protein, mouse
keywords: Cytokine; IL-1; IL-17; Inflammation; MCPIP1; MRNA Decay; Translation; mRNA
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