한빛사논문
Dongwan Kim1,2,5, Young-suk Lee1,2,5, Soo-Jin Jung1,2,5, Jinah Yeo1,2,3,5, Jenny J. Seo1,2, Young-Yoon Lee1,2, Jaechul Lim1,2,4, Hyeshik Chang1,2, Jaewon Song1,2, Jihye Yang1,2, Jong-Seo Kim1,2, Guhung Jung2, Kwangseok Ahn1,2 and V. Narry Kim1,2,*
1Center for RNA Research, Institute for Basic Science, Seoul, Republic of Korea. 2School of Biological Sciences, Seoul National University, Seoul, Republic of Korea. 3Present address: Center for Theragnosis, Biomedical Research Institute, Korea Institute of Science and Technology, Seoul, Republic of Korea. 4Present address: Department of Immunobiology, Yale University School of Medicine, New Haven, CT, USA. 5These authors contributed equally: Dongwan Kim, Young-suk Lee, Soo-Jin Jung, Jinah Yeo.
*Corresponding author
Abstract
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.
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TOP52020년 후보
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