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Viral hijacking of the TENT4-ZCCHC14 complex protects viral RNAs via mixed tailing.
Nature Structural & Molecular Biology ( IF 16.8 ) Pub Date : 2020-05-25 , DOI: 10.1038/s41594-020-0427-3
Dongwan Kim 1, 2 , Young-Suk Lee 1, 2 , Soo-Jin Jung 1, 2 , Jinah Yeo 1, 2, 3 , Jenny J Seo 1, 2 , Young-Yoon Lee 1, 2 , Jaechul Lim 1, 2, 4 , Hyeshik Chang 1, 2 , Jaewon Song 1, 2 , Jihye Yang 1, 2 , Jong-Seo Kim 1, 2 , Guhung Jung 2 , Kwangseok Ahn 1, 2 , V Narry Kim 1, 2
Affiliation  

TENT4 enzymes generate ‘mixed tails’ of diverse nucleotides at 3′ ends of RNAs via nontemplated nucleotide addition to protect messenger RNAs from deadenylation. Here we discover extensive mixed tailing in transcripts of hepatitis B virus (HBV) and human cytomegalovirus (HCMV), generated via a similar mechanism exploiting the TENT4–ZCCHC14 complex. TAIL-seq on HBV and HCMV RNAs revealed that TENT4A and TENT4B are responsible for mixed tailing and protection of viral poly(A) tails. We find that the HBV post-transcriptional regulatory element (PRE), specifically the CNGGN-type pentaloop, is critical for TENT4-dependent regulation. HCMV uses a similar pentaloop, an interesting example of convergent evolution. This pentaloop is recognized by the sterile alpha motif domain–containing ZCCHC14 protein, which in turn recruits TENT4. Overall, our study reveals the mechanism of action of PRE, which has been widely used to enhance gene expression, and identifies the TENT4–ZCCHC14 complex as a potential target for antiviral therapeutics.



中文翻译:

TENT4-ZCCHC14复合物的病毒劫持通过混合拖尾保护病毒RNA。

TENT4酶通过非模板核苷酸添加在RNA的3'端生成各种核苷酸的“混合尾巴”,以保护信使RNA免受腺苷酸化。在这里,我们发现乙肝病毒(HBV)和人类巨细胞病毒(HCMV)的转录本中存在广泛的混合拖尾,这是通过利用TENT4–ZCCHC14复合体的类似机制生成的。HBV和HCMV RNA的TAIL-seq显示TENT4A和TENT4B负责混合拖尾和保护病毒poly(A)尾巴。我们发现,HBV转录后调控元件(PRE),特别是CNGGN型五肽,对TENT4依赖性调控至关重要。HCMV使用类似的五分法,这是融合进化的有趣示例。这种五联征被含有无菌α基序结构域的ZCCHC14蛋白识别,该蛋白又募集了TENT4。总体,

更新日期:2020-05-25
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