Similar Datasets
Project description:TENT4 enzymes generate “mixed tails” on mRNAs by adding adenosines with intermittent non-adenosine residues, which protect mRNAs from deadenylation. Here we discover the extensive mixed tailing in the transcripts of two distinct DNA viruses, hepatitis B virus (HBV) and human cytomegalovirus (HCMV), and their striking similarity in the mechanism to exploit the TENT4-ZCCHC14 complex. TAIL-seq analyses of HBV and HCMV RNAs revealed that TENT4A and TENT4B are responsible for the mixed tailing and protection of viral poly(A) tails. By fCLIP-seq on HBV-producing cells, we found that the HBV posttranscriptional regulatory element (PRE) is the primary site of the TENT4 interactome. A hairpin with a CNGGN-type pentaloop in the PRE is critical for TENT4-dependent regulation. Unexpectedly, HCMV also utilizes a similar pentaloop hairpin, an interesting example of convergent evolution. We further found that the CNGGN pentaloop is recognized by the SAM domain-containing ZCCHC14 protein which in turn recruits TENT4 to stabilize viral transcripts. Altogether, our study reveals the action mechanism of PRE that has been widely used to enhance gene expression, and introduces the TENT4-ZCCHC14 complex as the key host factor and a potential target for antiviral therapeutics.
2020-04-27 | PXD018061 | Pride
Project description:TENT4 enzymes generate “mixed tails” on mRNAs by adding adenosines with intermittent non-adenosine residues, which protect mRNAs from deadenylation. Here we discover the extensive mixed tailing in the transcripts of two distinct DNA viruses, hepatitis B virus (HBV) and human cytomegalovirus (HCMV), and their striking similarity in the mechanism to exploit the TENT4-ZCCHC14 complex. TAIL-seq analyses of HBV and HCMV RNAs revealed that TENT4A and TENT4B are responsible for the mixed tailing and protection of viral poly(A) tails. By fCLIP-seq on HBV-producing cells, we found that the HBV posttranscriptional regulatory element (PRE) is the primary site of the TENT4 interactome. A hairpin with a CNGGN-type pentaloop in the PRE is critical for TENT4-dependent regulation. Unexpectedly, HCMV also utilizes a similar pentaloop hairpin, an interesting example of convergent evolution. We further found that the CNGGN pentaloop is recognized by the SAM domain-containing ZCCHC14 protein which in turn recruits TENT4 to stabilize viral transcripts. Altogether, our study reveals the action mechanism of PRE that has been widely used to enhance gene expression, and introduces the TENT4-ZCCHC14 complex as the key host factor and a potential target for antiviral therapeutics.
2020-03-09 | GSE146597 | GEO
Project description:TENT4 enzymes generate “mixed tails” on mRNAs by adding adenosines with intermittent non-adenosine residues, which protect mRNAs from deadenylation. Here we discover the extensive mixed tailing in the transcripts of two distinct DNA viruses, hepatitis B virus (HBV) and human cytomegalovirus (HCMV), and their striking similarity in the mechanism to exploit the TENT4-ZCCHC14 complex. TAIL-seq analyses of HBV and HCMV RNAs revealed that TENT4A and TENT4B are responsible for the mixed tailing and protection of viral poly(A) tails. By fCLIP-seq on HBV-producing cells, we found that the HBV posttranscriptional regulatory element (PRE) is the primary site of the TENT4 interactome. A hairpin with a CNGGN-type pentaloop in the PRE is critical for TENT4-dependent regulation. Unexpectedly, HCMV also utilizes a similar pentaloop hairpin, an interesting example of convergent evolution. We further found that the CNGGN pentaloop is recognized by the SAM domain-containing ZCCHC14 protein which in turn recruits TENT4 to stabilize viral transcripts. Altogether, our study reveals the action mechanism of PRE that has been widely used to enhance gene expression, and introduces the TENT4-ZCCHC14 complex as the key host factor and a potential target for antiviral therapeutics.
2020-03-09 | GSE146600 | GEO
Project description:Viral hijacking of the TENT4-ZCCHC14 complex protects viral RNAs via mixed tailing
| PRJNA611053 | ENA
Project description:Viral hijacking of the TENT4-ZCCHC14 complex protects viral RNAs via mixed tailing [fCLIP-seq]
| PRJNA611047 | ENA
Project description:Viral hijacking of the TENT4-ZCCHC14 complex protects viral RNAs via mixed tailing [TAIL-seq]
| PRJNA611056 | ENA
Project description:This SuperSeries is composed of the SubSeries listed below.
2019-06-09 | GSE116355 | GEO
Project description:The histone H3.3 chaperone DAXX is implicated in formation of heterochromatin and transcription silencing, especially for newly infecting DNA virus genomes entering the nucleus. Epstein-Barr virus (EBV) can efficiently establish stable latent infection as a chromatinized episome in the nucleus of infected cells. The EBV tegument BNRF1 is a DAXX-interacting protein required for the establishment of selective viral gene expression during latency. Here we report the structure of BNRF1 DAXX-interaction domain (DID) in complex with DAXX histone-binding domain (HBD) and histones H3.3-H4. BNRF1 DID contacts DAXX HBD and histones through non-conserved loops. The BNRF1-DAXX interface is responsible for BNRF1 localization to PML-nuclear bodies typically associated with host-antiviral resistance and transcriptional repression. Paradoxically, the interface is also required for selective transcription activation of viral latent cycle genes required for driving B-cell proliferation. These findings reveal molecular details of virus reprogramming of an antiviral histone chaperone to promote viral latency and cellular immortalization.
| S-EPMC5025803 | biostudies-literature
Project description:G protein-coupled receptors (GPCRs) constitute the largest family of molecules that transduce signals across the plasma membrane. Herpesviruses are successful pathogens that evolved diverse mechanisms to benefit their infection. Several human herpesviruses express GPCRs to exploit cellular signaling cascades during infection. These viral GPCRs demonstrate distinct biochemical and biophysical properties that result in the activation of a broad spectrum of signaling pathways. In immune-deficient individuals, human herpesvirus infection and the expression of their GPCRs are implicated in virus-associated diseases and pathologies. Emerging studies also uncover diverse mutations in components, particularly GPCRs and small G proteins, of GPCR signaling pathways that render the constitutive activation of proliferative and survival signal, which contributes to the oncogenesis of various human cancers. Hijacking GPCR-mediated signaling is a signature shared by diseases associated with constitutively active viral GPCRs and cellular mutations activating GPCR signaling, exposing key molecules that can be targeted for anti-viral and anti-tumor therapy.
| S-EPMC4972684 | biostudies-other
Project description:Proteins of the bromodomain and exterminal domain (BET) family mediate critical host functions such as cell proliferation, transcriptional regulation, and the innate immune response, which makes them preferred targets for viruses. These multidomain proteins are best known as transcriptional effectors able to read acetylated histone and non-histone proteins through their tandem bromodomains. They also contain other short motif-binding domains such as the extraterminal domain, which recognizes transcriptional regulatory proteins. Here, we describe how different viruses have evolved to hijack or disrupt host BET protein function through direct interactions with BET family members to support their own propagation. The network of virus-BET interactions emerges as highly intricate, which may complicate the use of small-molecule BET inhibitors-currently in clinical development for the treatment of cancer and cardiovascular diseases-to treat viral infections.
| S-EPMC9609653 | biostudies-literature