Post-translational modifications of hnRNP A1 differentially modulate retroviral IRES-mediated translation initiation.
Post-translational modifications of hnRNP A1 differentially modulate retroviral IRES-mediated translation initiation.
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DOI：
10.1093/nar/gkaa765
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发表时间：
2020-10-09
影响因子：
14.9
通讯作者：
López-Lastra M
中科院分区：
文献类型：
--
作者：
Barrera A;Ramos H;Vera-Otarola J;Fernández-García L;Angulo J;Olguín V;Pino K;Mouland AJ;López-Lastra M
人类免疫缺陷病毒1型(HIV-1)、人类T细胞嗜淋巴病毒1型(HTLV-1)和小鼠乳腺肿瘤病毒(MMTV)的全长mRNAs含有IRESS。逆转录病毒IRESS的活性需要IRES交易因子(ITAFs)，即hnRNP A1，已知的HIV-1 IRES的ITAFs。在本研究中，我们证明hnRNP A1也是HTLV-1和MMTV IRESS的ITAF。MMTV IRES对hnRNP A1的反应证明比HTLV-1或HIV-1 IRESS更敏感。还评估了hnRNP A1的翻译后修饰对HIV-1、HTLV-1和MMTV IRES活性的影响。结果表明，HIV-1和HTLV-1 IRESS对hnRNP A1及其磷酸化突变体S4A/S6A、S4D/S6D和S199A/D的反应相同，但S4D/S6D突变体刺激MMTV-IRES的活性显著高于野生型hnRNP A1。PRMT5诱导的hnRNP A1精氨酸残基的对称双甲基化使ITAF能够刺激HIV-1和HTLV-1 IRESS，同时降低了ITAF对MMTV IRES的刺激能力。我们得出结论，逆转录病毒IRES的活性不仅取决于招募的ITAFs，还取决于这些蛋白质在翻译后水平上的修饰方式。
The full-length mRNAs of the human immunodeficiency virus type-1 (HIV-1), the human T-cell lymphotropic virus type-1 (HTLV-1), and the mouse mammary tumor virus (MMTV) harbor IRESs. The activity of the retroviral-IRESs requires IRES-transacting factors (ITAFs), being hnRNP A1, a known ITAF for the HIV-1 IRES. In this study, we show that hnRNP A1 is also an ITAF for the HTLV-1 and MMTV IRESs. The MMTV IRES proved to be more responsive to hnRNP A1 than either the HTLV-1 or the HIV-1 IRESs. The impact of post-translational modifications of hnRNP A1 on HIV-1, HTLV-1 and MMTV IRES activity was also assessed. Results show that the HIV-1 and HTLV-1 IRESs were equally responsive to hnRNP A1 and its phosphorylation mutants S4A/S6A, S4D/S6D and S199A/D. However, the S4D/S6D mutant stimulated the activity from the MMTV-IRES to levels significantly higher than the wild type hnRNP A1. PRMT5-induced symmetrical di-methylation of arginine residues of hnRNP A1 enabled the ITAF to stimulate the HIV-1 and HTLV-1 IRESs while reducing the stimulatory ability of the ITAF over the MMTV IRES. We conclude that retroviral IRES activity is not only dependent on the recruited ITAFs but also relies on how these proteins are modified at the post-translational level.
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影响因子：
4.6
作者：
Cinti A;Le Sage V;Milev MP;Valiente-Echeverría F;Crossie C;Miron MJ;Panté N;Olivier M;Mouland AJ
通讯作者：
Mouland AJ
影响因子：
1.6
作者：
Black, AC;Luo, J;Rosenblatt, JD
通讯作者：
Rosenblatt, JD
影响因子：
3.7
作者：
Amorim R;Costa SM;Cavaleiro NP;da Silva EE;da Costa LJ
通讯作者：
da Costa LJ
影响因子：
14.9
作者：
Gao G;Dhar S;Bedford MT
通讯作者：
Bedford MT
影响因子：
5.4
作者：
Buck, CB;Shen, XF;Siliciano, RF
通讯作者：
Siliciano, RF