Viral hijacking of the TENT4-ZCCHC14 complex protects viral RNAs via mixed tailing

Cited 7 time in webofscience Cited 0 time in scopus
  • Hit : 53
  • Download : 0
Mixed tailing of hepatitis B virus and human cytomegalovirus transcripts via recruitment of the TENT4-ZCCHC14 complex by a common RNA element protects viral RNAs from degradation. 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.
Publisher
NATURE PUBLISHING GROUP
Issue Date
2020-06
Language
English
Article Type
Article
Citation

NATURE STRUCTURAL & MOLECULAR BIOLOGY, v.27, no.6, pp.581 - +

ISSN
1545-9993
DOI
10.1038/s41594-020-0427-3
URI
http://hdl.handle.net/10203/280413
Appears in Collection
BiS-Journal Papers(저널논문)
Files in This Item
There are no files associated with this item.
This item is cited by other documents in WoS
⊙ Detail Information in WoSⓡ Click to see webofscience_button
⊙ Cited 7 items in WoS Click to see citing articles in records_button

qr_code

  • mendeley

    citeulike


rss_1.0 rss_2.0 atom_1.0