LPS induces KH‐type splicing regulatory protein‐dependent processing of microRNA‐155 precursors in macrophages

Ruggiero, Tina; Trabucchi, Michèle; Santa, Francesca De; Zupo, Simona; Harfe, Brian D.; McManus, Michael T.; Rosenfeld, M G; Briata, Paola; Gherzi, Roberto

doi:10.1096/fj.09-131342

Cited by 187 publications

(167 citation statements)

References 41 publications

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“…On the other hand, most of the transcripts in Table 1 are not among the targets of KSRP destabilization identified earlier. This is not unexpected because the screen for increased ribosome association following KSRP depletion should not only detect mRNAs controlled by KSRP directly but also mRNAs that KSRP regulates indirectly by promoting maturation of miRNAs that target them (37,39). To what extent KSRP can restrict mRNA translation also independently of AREs and destabilization and of its effect on miRNA maturation is not clear at present.…”

Section: Discussionmentioning

confidence: 99%

Interleukin-1 Activates Synthesis of Interleukin-6 by Interfering with a KH-type Splicing Regulatory Protein (KSRP)-dependent Translational Silencing Mechanism

Dhamija

Kuehne

Winzen

et al. 2011

Journal of Biological Chemistry

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Inflammatory gene expression is controlled by post-transcriptional mechanisms. Many relevant transcripts contain AU-rich elements (AREs) 4 that can impose rapid degradation and restrict translation (1-3). Several proteins that interact with and mediate the effects of AREs have been identified. One of them, heterogeneous nuclear ribonucleoprotein K homology (KH)-type splicing regulatory protein (KSRP) is a member of the far upstream sequence element-binding proteins (4). It is a single-stranded nucleic acid-binding protein that contains four KH domains and has been reported to participate in transcription as well as splicing, editing, localization, and degradation of mRNAs and maturation of microRNA precursors (for a review, see Ref. 5). Most recently it has been found to contribute to regulation of RNA 3Ј-end processing (6).KSRP has been shown to facilitate mRNA degradation by directly binding to AREs and recruiting mRNA-degrading enzymes (7,8). Ksrp Ϫ/Ϫ cells and mice produce more type I interferons as a result of decreased mRNA decay and are refractory to viral infection (9). Different conditions of cellular activation or differentiation have been described to reduce KSRP binding and increase stability of specific mRNAs (e.g. Refs. 10 -13). The proinflammatory cytokine IL-1 can induce stabilization of KSRP target mRNAs, including that of IL-6 (14, 15), by reducing interaction of KSRP with the ARE presumably as a result of KSRP phosphorylation by p38 MAP kinase (10).IL-6, originally cloned as 26-kDa protein (16), IFN-␤2 (17), and BSF-2 (18), is a pleiotropic cytokine with important roles in inflammation, immune regulation, oncogenesis, and other physiological and pathological processes. Accordingly, interfering with IL-6 action is the aim of therapeutic strategies (19,20). IL-6 is induced in various cell types by a plethora of activators. Among the strongest and first identified are the proinflammatory cytokines tumor necrosis factor (TNF) (21) and IL-1 (22). Expression of IL-6 is controlled by transcriptional and post-transcriptional mechanisms. The latter involve AREs and a putative stem-loop structure that cause rapid degradation of the mRNA (23). Activators like IL-1 and lipopolysaccharide induce IL-6 mRNA stabilization through p38 MAPK/MK2 signaling (14, 24). IL-6 expression is also controlled by miRNAs (25,26).Our recent data showed that, in addition to stabilizing mRNAs, IL-1 can activate translation of mRNAs, including that of . We now provide evidence that repressed basal translation of IL-6 and a group of other mRNAs depends on KSRP. Interaction of KSRP with the IL-6 ARE is direct and is decreased in response to IL-1, suggesting a novel, miRNA-independent function for KSRP in translation.

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Section: Discussionmentioning

confidence: 99%

Interleukin-1 Activates Synthesis of Interleukin-6 by Interfering with a KH-type Splicing Regulatory Protein (KSRP)-dependent Translational Silencing Mechanism

Dhamija

Kuehne

Winzen

et al. 2011

Journal of Biological Chemistry

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“…Among them, the single-strand RNA binding protein KSRP (reviewed in Briata et al 26 ) interacts with the terminal loop of select miRNA precursors and promotes their maturation in cultured cells. [27][28][29] Importantly, KSRP has been shown to regulate gene expression also promoting the decay of inherently labile mRNAs in several cellular contexts including C2C12 myoblasts. 26 KSRP distinct functions are regulated by different protein kinases, including MAPK p38, PI3K/AKT and ATM.…”

mentioning

confidence: 99%

PI3K/AKT signaling determines a dynamic switch between distinct KSRP functions favoring skeletal myogenesis

Briata¹,

Lin

Giovarelli

et al. 2011

Cell Death Differ

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Skeletal myogenesis is orchestrated by distinct regulatory signaling pathways, including PI3K/AKT, that ultimately control muscle gene expression. Recently discovered myogenic micro-RNAs (miRNAs) are deeply implicated in muscle biology. Processing of miRNAs from their primary transcripts is emerging as a major step in the control of miRNA levels and might be well suited to be regulated by extracellular signals. Here we report that the RNA binding protein KSRP is required for the correct processing of primary myogenic miRNAs upon PI3K/AKT activation in myoblasts C2C12 and in the course of injury-induced muscle regeneration, as revealed by Ksrp knock-out mice analysis. PI3K/AKT activation regulates in opposite ways two distinct KSRP functions inhibiting its ability to promote decay of myogenin mRNA and activating its ability to favor maturation of myogenic miRNAs. This dynamic regulatory switch eventually contributes to the activation of the myogenic program.

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“…In the monocytic lineage, miR-155 was shown to be up-regulated by proinflammatory LPS and TNF-α (16)(17)(18)(19), playing an important role in monocyte proliferation, and in macrophage and dendritic cell differentiation (15)(16)(17)(18)(19)(20)(21). However, the roles of miR-155 in the osteoclast trajectory, derived from the same monocytic precursor, were not known until now.…”

mentioning

confidence: 99%

miRNA-based mechanism for the commitment of multipotent progenitors to a single cellular fate

Mann

Barad²,

Agami

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

102

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When stem cells and multipotent progenitors differentiate, they undergo fate restriction, enabling a single fate and blocking differentiation along alternative routes. We herein present a mechanism whereby such unequivocal commitment is achieved, based on micro-RNA (miRNA)-dependent repression of an alternative cell fate. We show that the commitment of monocyte RAW264.7 progenitors to active macrophage differentiation involves rapid up-regulation of miR-155 expression, which leads to the suppression of the alternative pathway, namely RANK ligand-induced osteoclastogenesis, by repressing the expression of MITF, a transcription factor essential for osteoclast differentiation. A temporal asymmetry, whereby miR-155 expression precedes and overrides the activation of the osteoclast transcriptional program, provides the means for coherent macrophage differentiation, even in the presence of osteoclastogenic signals. Based on these findings, we propose that miRNA may provide a general mechanism for the unequivocal commitment underlying stem cell differentiation.

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LPS induces KH‐type splicing regulatory protein‐dependent processing of microRNA‐155 precursors in macrophages

Cited by 187 publications

References 41 publications

Interleukin-1 Activates Synthesis of Interleukin-6 by Interfering with a KH-type Splicing Regulatory Protein (KSRP)-dependent Translational Silencing Mechanism

Interleukin-1 Activates Synthesis of Interleukin-6 by Interfering with a KH-type Splicing Regulatory Protein (KSRP)-dependent Translational Silencing Mechanism

PI3K/AKT signaling determines a dynamic switch between distinct KSRP functions favoring skeletal myogenesis

miRNA-based mechanism for the commitment of multipotent progenitors to a single cellular fate

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