Human lysyl-tRNA synthetase phosphorylation promotes HIV-1 proviral DNA transcription.
Human lysyl-tRNA synthetase phosphorylation promotes HIV-1 proviral DNA transcription.
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DOI：
10.1093/nar/gkad941
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发表时间：
2023-12-11
影响因子：
14.9
通讯作者：
Musier-Forsyth, Karin
中科院分区：
文献类型：
--
作者：
Tang, Yingke;Behrens, Ryan T.;St Gelais, Corine;Wu, Siqi;Vivekanandan, Saravanan;Razin, Ehud;Fang, Pengfei;Wu, Li;Sherer, Nathan;Musier-Forsyth, Karin
人赖氨酰-tRNA合成酶（LysRS）先前显示从其在多氨酰-tRNA合成酶复合物（MSC）中的正常细胞质位置重新定位到HIV-1感染细胞的细胞核。核定位依赖于S207磷酸化，但pS207-LysRS在HIV-1生命周期中的核功能尚不清楚。在这里，我们表明，在CRISPR/Cas9产生的S207 A-LysRS敲入细胞系中，HIV-1复制严重减少;这种效应被S207 D-LysRS拯救。LysRS磷酸化上调HIV-1转录，正如直接转染Ap 4A一样，Ap 4A是由pS207-LysRS合成的上游转录因子2（USF 2）激活剂。过表达已知稳定LysRS MSC结合的MSC衍生肽抑制HIV-1复制。HIV-1前病毒DNA和其他USF 2靶基因的转录在肽表达细胞中减少。我们提出核pS207-LysRS产生Ap 4A，导致HIV-1转录的激活。我们的研究结果表明，核LysRS在促进HIV-1复制和抗病毒治疗的新途径的新作用。
Human lysyl-tRNA synthetase (LysRS) was previously shown to be re-localized from its normal cytoplasmic location in a multi-aminoacyl-tRNA synthetase complex (MSC) to the nucleus of HIV-1 infected cells. Nuclear localization depends on S207 phosphorylation but the nuclear function of pS207-LysRS in the HIV-1 lifecycle is unknown. Here, we show that HIV-1 replication was severely reduced in a S207A-LysRS knock-in cell line generated by CRISPR/Cas9; this effect was rescued by S207D-LysRS. LysRS phosphorylation up-regulated HIV-1 transcription, as did direct transfection of Ap4A, an upstream transcription factor 2 (USF2) activator that is synthesized by pS207-LysRS. Overexpressing an MSC-derived peptide known to stabilize LysRS MSC binding inhibited HIV-1 replication. Transcription of HIV-1 proviral DNA and other USF2 target genes was reduced in peptide-expressing cells. We propose that nuclear pS207-LysRS generates Ap4A, leading to activation of HIV-1 transcription. Our results suggest a new role for nuclear LysRS in facilitating HIV-1 replication and new avenues for antiviral therapy.
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DOI：
10.1261/rna.057299.116
发表时间：
2016-08
期刊：
RNA (New York, N.Y.)
影响因子：
--
作者：
Eckwahl MJ;Arnion H;Kharytonchyk S;Zang T;Bieniasz PD;Telesnitsky A;Wolin SL
通讯作者：
Wolin SL
影响因子：
3.5
作者：
Kleiman L;Jones CP;Musier-Forsyth K
通讯作者：
Musier-Forsyth K
影响因子：
5.3
作者：
Lee, YN;Razin, E
通讯作者：
Razin, E
影响因子：
14.8
作者：
Guo, Min;Schimmel, Paul
通讯作者：
Schimmel, Paul
影响因子：
--
作者：
Boulos S;Park MC;Zeibak M;Foo SY;Jeon YK;Kim YT;Motzik A;Tshori S;Hamburger T;Kim S;Nechushtan H;Razin E
通讯作者：
Razin E