SAMHD1 … and Viral Ways around It

Deutschmann, Janina; Gramberg, Thomas

doi:10.3390/v13030395

Cited by 19 publications

(14 citation statements)

References 152 publications

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“…TRIM25-mediated ubiquitination of RTRAF may affect its ability to do so. The novel bona fide TRIM25 substrate NME1, which functions as a major synthesizer of non-ATP nucleoside triphosphates, upon ubiquitination may inhibit alphavirus replication via a similar mechanism as the potent restriction factor SAMHD1, which depletes deoxynucleotide pools, effectively preventing replication of varied DNA viruses and reverse transcription of HIV-1 [73]. On the other hand, TRIM25-mediated ubiquitination of NME1 may inhibit its metastatic suppressor activities, potentially serving as a novel mechanism for TRIM25's previously described roles in carcinogenesis.…”

Section: Plos Pathogensmentioning

confidence: 99%

Elucidation of TRIM25 ubiquitination targets involved in diverse cellular and antiviral processes

et al. 2022

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The tripartite motif (TRIM) family of E3 ubiquitin ligases is well known for its roles in antiviral restriction and innate immunity regulation, in addition to many other cellular pathways. In particular, TRIM25-mediated ubiquitination affects both carcinogenesis and antiviral response. While individual substrates have been identified for TRIM25, it remains unclear how it regulates diverse processes. Here we characterized a mutation, R54P, critical for TRIM25 catalytic activity, which we successfully utilized to “trap” substrates. We demonstrated that TRIM25 targets proteins implicated in stress granule formation (G3BP1/2), nonsense-mediated mRNA decay (UPF1), nucleoside synthesis (NME1), and mRNA translation and stability (PABPC4). The R54P mutation abolishes TRIM25 inhibition of alphaviruses independently of the host interferon response, suggesting that this antiviral effect is a direct consequence of ubiquitination. Consistent with that, we observed diminished antiviral activity upon knockdown of several TRIM25-R54P specific interactors including NME1 and PABPC4. Our findings highlight that multiple substrates mediate the cellular and antiviral activities of TRIM25, illustrating the multi-faceted role of this ubiquitination network in modulating diverse biological processes.

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Section: Plos Pathogensmentioning

confidence: 99%

Elucidation of TRIM25 ubiquitination targets involved in diverse cellular and antiviral processes

et al. 2022

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“…The SAM domain and HD domain-containing protein 1 (SAMHD1) are some of the most well-known protective factors of innate immunity, inhibiting the replication of viruses and participating in the repression of both L1 and other retroelements [344]. The mechanism of inhibition of L1 differs from the antiviral inhibition and is observed in dividing cells [316].…”

Section: Interferon-induced Factors Inhibiting the Formation Of L1 Rnpmentioning

confidence: 99%

Factors Regulating the Activity of LINE1 Retrotransposons

Protasova

Andreeva

Rogaev

2021

Genes

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LINE-1 (L1) is a class of autonomous mobile genetic elements that form somatic mosaicisms in various tissues of the organism. The activity of L1 retrotransposons is strictly controlled by many factors in somatic and germ cells at all stages of ontogenesis. Alteration of L1 activity was noted in a number of diseases: in neuropsychiatric and autoimmune diseases, as well as in various forms of cancer. Altered activity of L1 retrotransposons for some pathologies is associated with epigenetic changes and defects in the genes involved in their repression. This review discusses the molecular genetic mechanisms of the retrotransposition and regulation of the activity of L1 elements. The contribution of various factors controlling the expression and distribution of L1 elements in the genome occurs at all stages of the retrotransposition. The regulation of L1 elements at the transcriptional, post-transcriptional and integration into the genome stages is described in detail. Finally, this review also focuses on the evolutionary aspects of L1 accumulation and their interplay with the host regulation system.

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“…The novel bona fide TRIM25 substrate NME1, which functions as a major synthesizer of non-ATP nucleoside triphosphates, upon ubiquitination may inhibit alphavirus replication via a similar mechanism as the potent restriction factor SAMHD1, which depletes deoxynucleotide pools, effectively preventing replication of varied DNA viruses and reverse transcription of HIV-1. 63 On the other hand, TRIM25-mediated ubiquitination of NME1 may inhibit its metastatic suppressor activities, potentially serving as a novel mechanism for TRIM25’s previously described roles in carcinogenesis. Further studies need to be carried out to elucidate the functional consequences of these TRIM25 substrates in blocking viral translation and other cellular processes.…”

Section: Discussionmentioning

confidence: 99%

Substrate trapping approach identifies TRIM25 ubiquitination targets involved in diverse cellular and antiviral processes

Yang

Huang

Jami‐Alahmadi

et al. 2022

Preprint

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The tripartite motif (TRIM) family of E3 ubiquitin ligases is well known for its roles in antiviral restriction and innate immunity regulation, in addition to many other cellular pathways. In particular, TRIM25-mediated ubiquitination affects both carcinogenesis and antiviral response. While individual substrates have been identified for TRIM25, it remains unclear how it regulates diverse processes. Here we characterized a mutation, R54P, critical for TRIM25 catalytic activity, which we successfully utilized to "trap" substrates. We demonstrated that TRIM25 targets proteins implicated in stress granule formation (G3BP1/2), nonsense-mediated mRNA decay (UPF1), and nucleoside synthesis (NME1). R54P abolishes TRIM25 inhibition of alphaviruses independently of the host interferon response, suggesting that this antiviral effect is a direct consequence of ubiquitination. Consistent with that, we observed diminished antiviral activity upon knockdown of several TRIM25-R54P specific interactors including NME1. Our findings highlight that multiple substrates mediate the cellular and antiviral activities of TRIM25, illustrating the multi-faceted role of this ubiquitination network in diverse biological processes.

show abstract

SAMHD1 … and Viral Ways around It

Cited by 19 publications

References 152 publications

Elucidation of TRIM25 ubiquitination targets involved in diverse cellular and antiviral processes

Elucidation of TRIM25 ubiquitination targets involved in diverse cellular and antiviral processes

Factors Regulating the Activity of LINE1 Retrotransposons

Substrate trapping approach identifies TRIM25 ubiquitination targets involved in diverse cellular and antiviral processes

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