Activation of the interferon system during myogenesis in vitro

Birnbaum, Miriam; Trink, Barry; Shainberg, Asher; Salzberg, Samuel

doi:10.1111/j.1432-0436.1990.tb00467.x

Cited by 19 publications

(16 citation statements)

References 46 publications

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“…2-5A-synthetase is induced in rat and mouse myoblasts (4). PKR is induced after the shift of mouse C2C12 myoblasts to differentiating conditions.…”

Section: Discussionmentioning

confidence: 94%

“…Indeed, expression of IFN-inducible proteins, such as 2-5A-synthetase, doublestanded RNA-activated protein kinase (PKR), and p202 (a member of the "200 family" of murine proteins) have been observed during myoblast differentiation (4,9,38). Recently, Kronfeld et al (23) established the involvement of PKR in the regulation of myogenesis using PKR transfected C2C12 cells.…”

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confidence: 99%

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The 2′-5′ Oligoadenylate/RNase L/RNase L Inhibitor Pathway Regulates Both MyoD mRNA Stability and Muscle Cell Differentiation

Bisbal

Silhol

Laubenthal

et al. 2000

Molecular and Cellular Biology

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The 2-5 oligoadenylate (2-5A)/RNase L pathway is one of the enzymatic pathways induced by interferon. RNase L is a latent endoribonuclease which is activated by 2-5A and inhibited by a specific protein known as RLI (RNase L inhibitor). This system has an important role in regulating viral infection. Additionally, variations in RNase L activity have been observed during cell growth and differentiation but the significance of the 2-5A/RNase L/RLI pathway in these latter processes is not known. To determine the roles of RNase L and RLI in muscle differentiation, C2 mouse myoblasts were transfected with sense and antisense RLI cDNA constructs. Importantly, the overexpression of RLI in C2 cells was associated with diminished RNase L activity, an increased level of MyoD mRNA, and accelerated kinetics of muscle differentiation. Inversely, transfection of the RLI antisense construct was associated with increased RNase L activity, a diminished level of MyoD mRNA, and delayed differentiation. In agreement with these data, MyoD mRNA levels were also decreased in C2 cells transfected with an inducible RNase L construct. The effect of RNase L activity on MyoD mRNA levels was relatively specific because expression of several other mRNAs was not altered in C2 transfectants. Therefore, RNase L is directly involved in myoblast differentiation, probably through its role in regulating MyoD stability. This is the first identification of a potential mRNA target for RNase L.The 2Ј-5Ј oligoadenylate (2-5A)/RNase L system is an interferon (IFN)-inducible RNA degradation pathway which is responsible for many of the antiviral and antiproliferative effects of IFNs (37, 41).The 2-5A pathway is composed of at least three types of enzymatic activities: 2-5A-synthetase, 2-5A-degrading enzymes, and RNase L. 2-5A, an oligoadenylate with 2Ј-5Ј phosphodiester bonds, activates RNase L (53), a latent endoribonuclease. Upon activation, RNase L cleaves mRNAs 3Ј of UpNp sequences, thus leading to the inhibition of protein synthesis (14,21).The activity of RNase L was originally thought to be modulated solely by the concentration of the 2-5A activator (11,21). Moreover, we have previously established that RNase L activity can also be regulated by RLI (RNase L inhibitor), a protein inhibitor (5). Overexpression of the RLI cDNA in HeLa cells results in the inhibition of the IFN-activated 2-5A pathway. RLI is induced by viruses such as encephalomyocarditis virus (EMCV) and human immunodeficiency virus (HIV), causing an inhibition of the 2-5A/RNase L system (27, 28). The role of the 2-5A/RNase L pathway in the selective reduction of viral mRNA during EMCV and HIV infection has been demonstrated elsewhere (16,25,27).Variations in intracellular 2-5A and 2-5A-synthetase levels have been observed during cell growth and differentiation even in the absence of exogenous IFN treatment. Indeed, expression of IFN-inducible proteins, such as 2-5A-synthetase, doublestanded RNA-activated protein kinase (PKR), and p202 (a member of the "200 family" of murine proteins) h...

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“…2-5A-synthetase is induced in rat and mouse myoblasts (4). PKR is induced after the shift of mouse C2C12 myoblasts to differentiating conditions.…”

Section: Discussionmentioning

confidence: 94%

mentioning

confidence: 99%

The 2′-5′ Oligoadenylate/RNase L/RNase L Inhibitor Pathway Regulates Both MyoD mRNA Stability and Muscle Cell Differentiation

Bisbal

Silhol

Laubenthal

et al. 2000

Molecular and Cellular Biology

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“…It is of interest that several interferon-inducible proteins (in addition to p204 and p202a) have been reported to be induced during myoblast differentiation (6,69). These interferon-inducible proteins include 2Ј-5Ј oligoadenylate synthetase and RNA-activatable protein kinase (PKR).…”

Section: Discussionmentioning

confidence: 99%

MyoD-Dependent Induction during Myoblast Differentiation of p204, a Protein Also Inducible by Interferon

Liu

Wang

Zhao

et al. 2000

Molecular and Cellular Biology

129

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p204, an interferon-inducible p200 family protein, inhibits rRNA synthesis in fibroblasts by blocking the binding of the upstream binding factor transcription factor to DNA. Here we report that among 10 adult mouse tissues tested, the level of p204 was highest in heart and skeletal muscles. In cultured C2C12 skeletal muscle myoblasts, p204 was nucleoplasmic and its level was low. During myoblast fusion this level strongly increased, p204 became phosphorylated, and the bulk of p204 appeared in the cytoplasm of the myotubes. Leptomycin B, an inhibitor of nuclear export that blocked myoblast fusion, inhibited the nuclear export signal-dependent translocation of p204 to the cytoplasm. The increase in the p204 level during myoblast fusion was a consequence of MyoD transcription factor binding to several MyoD-specific sequences in the gene encoding p204, followed by transcription. Overexpression of p204 (in C2C12 myoblasts carrying an inducible p204 expression plasmid) accelerated the fusion of myoblasts to myotubes in differentiation medium and induced the fusion even in growth medium. The level of p204 in mouse heart muscle strongly increased during differentiation; it was barely detectable in 10.5-day-old embryos, reached the peak level in 16.5-day-old embryos, and remained high thereafter. p204 is the second p200 family protein (after p202a) found to be involved in muscle differentiation.

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“…The activities of some other interferon-inducible proteins, e.g., 2Ј,5Ј-oligoadenylate synthetases and double-stranded RNA-activatable protein kinase, were reported to increase transiently during the fusion of rat thigh muscle cells in vitro (8).…”

Section: Discussionmentioning

confidence: 99%

Increase in p202 Expression during Skeletal Muscle Differentiation: Inhibition of MyoD Protein Expression and Activity by p202

Datta

Wang

Burma

et al. 1998

Molecular and Cellular Biology

105

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Activation of the interferon system during myogenesis in vitro

Cited by 19 publications

References 46 publications

The 2′-5′ Oligoadenylate/RNase L/RNase L Inhibitor Pathway Regulates Both MyoD mRNA Stability and Muscle Cell Differentiation

The 2′-5′ Oligoadenylate/RNase L/RNase L Inhibitor Pathway Regulates Both MyoD mRNA Stability and Muscle Cell Differentiation

MyoD-Dependent Induction during Myoblast Differentiation of p204, a Protein Also Inducible by Interferon

Increase in p202 Expression during Skeletal Muscle Differentiation: Inhibition of MyoD Protein Expression and Activity by p202

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