The role of mouse 2′,5′-oligoadenylate synthetase 1 paralogs

Elkhateeb, Enas Hamed Mahmoud; Tag-EL-Din-Hassan, Hassan T.; Sasaki, Nobuya; Torigoe, Daisuke; Morimatsu, Masami; Agui, Takashi

doi:10.1016/j.meegid.2016.09.018

Cited by 26 publications

(15 citation statements)

References 33 publications

(33 reference statements)

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“…Of particular interest is that the five target genes were immune response genes. Ifit3 and Oas1g have antiviral functions in some tissues including the lung and liver ( 56 , 57 ), and Tgtp2, Ifi47 , and Gbp3 contributes to defense against bacteria and protozoa ( 58 – 60 ). Interestingly, Ifi47 and Gbp3 were reported to play some roles in defense against Toxoplasma Gondii ( 58 , 60 ), which could impair spermatogenesis by infecting the rat testis ( 61 ).…”

Section: Discussionmentioning

confidence: 99%

A Testis-Specific Long Non-Coding RNA, lncRNA-Tcam1, Regulates Immune-Related Genes in Mouse Male Germ Cells

et al. 2017

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Spermatogenesis is precisely controlled by hormones from the hypothalamus–pituitary–gonadal axis and testis-specific genes, but the regulatory mechanism is not fully understood. Recently, a large number of long non-coding RNAs (lncRNAs) are found to be transcribed at each stage of meiosis of male germ cells, and their functions in spermatogenesis have yet to be fully investigated. lncRNA-testicular cell adhesion molecule 1 (lncRNA-Tcam1) is a nuclear lncRNA which is specifically expressed in mouse male germ cells and presumed to play a role in gene regulation during meiosis. Here, we present the identification of potential target genes of lncRNA-Tcam1 using spermatocyte-derived GC-2spd(ts) cells. Initially, 55 target gene candidates were detected by RNA-sequencing of two GC-2spd(ts) cell clones that were stably transfected with transgenes to express lncRNA-Tcam1 at different levels. Expression of 21 genes of the candidates was found to be correlated with lncRNA-Tcam1 at 7–14 postnatal days, when lncRNA-Tcam1 expression was elevated. Subsequently, we examined expression levels of the 21 genes in other two GC-2spd(ts) clones, and 11 genes exhibited the correlation with lncRNA-Tcam1. Induction of lncRNA-Tcam1 transcription using the Tet-off system verified that six genes, Trim30a, Ifit3, Tgtp2, Ifi47, Oas1g, and Gbp3, were upregulated in GC-2spd(ts) cells, indicating that lncRNA-Tcam1 is responsible for the regulation of gene expression of the six genes. In addition, five of the six genes, namely, Ifit3, Tgtp2, Ifi47, Oas1g, and Gbp3, are immune response genes, and Trim30a is a negative regulator of immune response. Altogether, the present study suggests that lncRNA-Tcam1 is responsible for gene regulation for the immune response during spermatogenesis.

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Section: Discussionmentioning

confidence: 99%

A Testis-Specific Long Non-Coding RNA, lncRNA-Tcam1, Regulates Immune-Related Genes in Mouse Male Germ Cells

et al. 2017

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“…Although humans have a single Oas1 gene, in mice the Oas1 gene locus underwent a series of 53 duplication events leading to the existence of eight Oas1 paralogues. Of the paralogues, only OAS1a 54 and OAS1g have been shown to be enzymatically active, with OAS1g producing significantly more 55 oligoadenylates as compared to OAS1a (Kakuta et al 2002;Elkhateeb et al 2016). We show that 56 removal of the Oas1g alternative splice site in a murine macrophage cell line leads to increased 57 expression of Oas1g, both in stimulated and unstimulated conditions.…”

Section: Introduction 24mentioning

confidence: 80%

Alternative splicing coupled with transcript degradation modulates OAS1g antiviral activity

Frankiw

Mann

et al. 2019

RNA

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1At the heart of an innate immune response lies a tightly regulated gene expression program. This 2 precise regulation is crucial because small changes can shift the balance from protective to 3 destructive immunity. Here we identify a frequently used alternative splice site in the gene 4 oligoadenylate synthetase 1g (Oas1g), a key component of the 2-5A antiviral system. Usage of this 5 splice site leads to the generation of a transcript subject to decay, and removal of the site leads to 6 increased expression of Oas1g and an improved antiviral response. However, removal of the splice 7 site also leads to an increase in apoptotic cell death, suggesting this splicing event exists as a 8 compromise between the pathogen protective benefits and collateral damage associated with OAS1g 9 activity. Across the innate immune response, we show a multitude of alternative splicing events 10 predicted to lead to decay exist and thus, have the potential to play a significant role in the regulation 11 of gene expression in innate immunity.

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“…Oas1a is a 2',5'-oligoadenylate synthase that synthesizes higher oligomers of 2'-5'-oligoadenylates from ATP. The oligoadenylates activate RNase L, which degrades viral RNAs (48). Oral administration of LC-plasma significantly enhanced Mx1 and Oas1a and non-significantly enhanced Viperin and Isg15 in the spleen.…”

Section: Discussionmentioning

confidence: 99%

Administration of plasmacytoid dendritic cell-stimulative lactic acid bacteria is effective against dengue virus infection in mice

et al. 2018

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dengue virus (dENV), a mosquito-borne flavivirus, causes an acute febrile illness that is a major public health problem in the tropics and subtropics globally. However, methods to prevent or treat dENV infection have not been well established. It was previously demonstrated that Lactococcus lactis strain plasma (Lc-plasma) has the ability to stimulate plasmacytoid dendritic cells (pdcs). As pdcs are key immune cells that control viral infection by producing large amounts of type I interferons (IFN), the present study evaluated the effect of Lc-plasma on dENV infection using a mouse infectious dENV strain. Mice were divided into two groups and the test group was orally administered Lc-plasma for two weeks. Two weeks following administration, the mice were infected with dENV and the relative viral titers and the expression of the inflammatory genes in DENV-infected tissue were measured using reverse transcription-quantitative polymerase chain reaction (RT-qPcR). The relative viral titers were notably lower in the dENV-infected tissues compared with the control group when Lc-plasma was orally administered prior to dENV infection. Furthermore, the expression of the inflammatory genes associated with DENV infection was also reduced by Lc-plasma administration. To investigate how Lc-plasma administration controls dENV infection, the present study examined anti-viral gene expression, which is critical for the viral clearance induced by type I IFN. Two weeks subsequent to the administration of Lc-plasma, the expression of anti-viral gene was measured using RT-qPcR. Oral intake of Lc-plasma enhanced anti-viral gene expression in dENV-infected spleen tissue. To clarify the detailed mechanism, in vitro co-culture studies using bone-marrow derived dc (BMdc) were performed. BMdc were stimulated with Lc-plasma in combination with anti-IFN-α/β antibody and the expression of anti-viral genes was measured. In vitro studies revealed that the effect of Lc-plasma on anti-viral genes was dependent on type I IFN. Based on these results, Lc-plasma may be effective against dENV infection by stimulating pdcs, which results in the increased production of anti-viral factors.

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The role of mouse 2′,5′-oligoadenylate synthetase 1 paralogs

Cited by 26 publications

References 33 publications

A Testis-Specific Long Non-Coding RNA, lncRNA-Tcam1, Regulates Immune-Related Genes in Mouse Male Germ Cells

A Testis-Specific Long Non-Coding RNA, lncRNA-Tcam1, Regulates Immune-Related Genes in Mouse Male Germ Cells

Alternative splicing coupled with transcript degradation modulates OAS1g antiviral activity

Administration of plasmacytoid dendritic cell-stimulative lactic acid bacteria is effective against dengue virus infection in mice

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