Institut de Biologie Structurale, Univ Grenoble Alpes, CEA, CNRS, IBS, Grenoble, France.
Swiss-Prot Group, Swiss Institute of Bioinformatics, Centre Médicale Universitaire, Geneva, Switzerland.
PLoS Pathog. 2020 Nov 5;16(11):e1008972. doi: 10.1371/journal.ppat.1008972. eCollection 2020 Nov.
Paramyxo- and filovirus nucleocapsids (NCs) have bipartite promoters at their 3' ends to initiate RNA synthesis. The 2 elements, promoter element 1 (PE1) and promoter element 2 (PE2), are separated by a spacer region that must be exactly a multiple of 6 nucleotides (nt) long. Paramyxovirus NCs have 13 nucleoprotein (NP) subunits/turn, such that PE1 and PE2 are juxtaposed on the same face of the NC helix, for concerted recognition by the viral polymerase. Ebola virus (EBOV) NCs, in contrast, have 25 to 28 subunits/turn, meaning that PE1 and PE2 cannot be juxtaposed. However, there is evidence that the number of subunits/turn at the 3' end of the EBOV NC is variable. We propose a paramyxovirus-like model for EBOV explaining why there are 8 contiguous copies of the PE2 repeat when 3 are sufficient, why expanding this run to 13 further improves minigenome performance, and why there is a limit to the number of hexa-nt that can be inserted in the spacer region.
副黏病毒和丝状病毒核衣壳(NC)在其 3' 末端具有二分启动子,以启动 RNA 合成。这两个元件,启动子元件 1(PE1)和启动子元件 2(PE2),由一个间隔区隔开,该间隔区必须正好是 6 个核苷酸(nt)的倍数长。副黏病毒 NC 具有 13 个核蛋白(NP)亚基/圈,因此 PE1 和 PE2 并列在 NC 螺旋的同一面上,以便病毒聚合酶协同识别。相比之下,埃博拉病毒(EBOV)NC 具有 25 到 28 个亚基/圈,这意味着 PE1 和 PE2 不能并列。然而,有证据表明 EBOV NC 3' 末端的亚基数是可变的。我们提出了一种类似于副黏病毒的 EBOV 模型,解释了为什么在 3 个重复足以满足要求的情况下,PE2 重复有 8 个连续拷贝,为什么将此重复扩展到 13 个进一步提高了小基因组的性能,以及为什么插入间隔区的六聚体 nt 数量有限。