PML and PML-like exonucleases restrict retrotransposons in jawed vertebrates.

PML and PML-like exonucleases restrict retrotransposons in jawed vertebrates.
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DOI:
10.1093/nar/gkad152
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发表时间:
2023-04-24
影响因子:
14.9
通讯作者:
Dellaire, Graham
Dellaire, Graham
中科院分区:
生物学2区
文献类型:
--
作者:
Mathavarajah, Sabateeshan;Vergunst, Kathleen L.;Habib, Elias B.;Williams, Shelby K.;He, Raymond;Maliougina, Maria;Park, Mika;Salsman, Jayme;Roy, Stephane;Braasch, Ingo;Roger, Andrew J.;Langelaan, David N.;Dellaire, Graham

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我们已经发现了早幼粒细胞白血病(PML)基因和新型PML样DEDDh核酸外切酶在有颌脊椎动物中通过限制LINE-1(L1)逆转录转座维持基因组稳定性中的作用。虽然哺乳动物PML蛋白形成核小体,但我们发现斑点雀鳝PML直系同源物和鱼类中的相关蛋白作为细胞质DEDDh核酸外切酶发挥功能。与此相反,PML蛋白质从马属物种定位到细胞质和形成核体。我们还确定了PML样外显子9(Plex 9)基因在硬骨鱼编码核酸外切酶。Plex 9蛋白类似于TREX 1,但在TREX家族中是独特的,并且与gar PML具有同源性。我们还表征了TREX 1和美西螈中第一个非哺乳动物TREX 1同源物的分子进化。在趋同进化的一个例子中,与TREX 1类似,gar PML和斑马鱼Plex 9蛋白抑制L1逆转录转座,并可以补充哺乳动物细胞中的TREX 1敲除。出口到细胞质后,人PML-I亚型也限制L1通过其保守的C-末端,通过泛素-蛋白酶体系统增强ORF 1 p降解。因此,PML最初是作为逆转录因子的细胞质抑制因子出现的,尽管它在核体的组装中发挥了新的作用,但这种功能在黑猩猩中仍然保留。
We have uncovered a role for the promyelocytic leukemia (PML) gene and novel PML-like DEDDh exonucleases in the maintenance of genome stability through the restriction of LINE-1 (L1) retrotransposition in jawed vertebrates. Although the mammalian PML protein forms nuclear bodies, we found that the spotted gar PML ortholog and related proteins in fish function as cytoplasmic DEDDh exonucleases. In contrast, PML proteins from amniote species localized both to the cytoplasm and formed nuclear bodies. We also identified the PML-like exon 9 (Plex9) genes in teleost fishes that encode exonucleases. Plex9 proteins resemble TREX1 but are unique from the TREX family and share homology to gar PML. We also characterized the molecular evolution of TREX1 and the first non-mammalian TREX1 homologs in axolotl. In an example of convergent evolution and akin to TREX1, gar PML and zebrafish Plex9 proteins suppressed L1 retrotransposition and could complement TREX1 knockout in mammalian cells. Following export to the cytoplasm, the human PML-I isoform also restricted L1 through its conserved C-terminus by enhancing ORF1p degradation through the ubiquitin-proteasome system. Thus, PML first emerged as a cytoplasmic suppressor of retroelements, and this function is retained in amniotes despite its new role in the assembly of nuclear bodies.
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