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Mechanisms of Retrovirus-induced Cancers01:51

Mechanisms of Retrovirus-induced Cancers

Retroviruses are RNA viruses that have been shown to cause cancers in diverse species, including chickens, mice, cats, and monkeys. The RNA genomes of these viruses are first reverse-transcribed into single and then double-stranded DNA (dsDNA) copies. This dsDNA called proviral DNA then integrates into the host genome. Subsequently, the host cell transcribes the proviral DNA in concert with the chromosomal DNA. This leads to the production of viral RNA and proteins that assemble at the host...
Mechanisms of Retrovirus-induced Cancers01:51

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Retroviruses are RNA viruses that have been shown to cause cancers in diverse species, including chickens, mice, cats, and monkeys. The RNA genomes of these viruses are first reverse-transcribed into single and then double-stranded DNA (dsDNA) copies. This dsDNA called proviral DNA then integrates into the host genome. Subsequently, the host cell transcribes the proviral DNA in concert with the chromosomal DNA. This leads to the production of viral RNA and proteins that assemble at the host...
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Rous Sarcoma virus or RSV was discovered by F. Peyton Rous in the year 1911 as a filterable transmissible agent that could cause tumors in chickens. He won a Nobel Prize for this discovery in 1966. His experiments clearly demonstrated that some cancers could be caused by infectious agents and led to the discovery of many more cancer-causing viruses in animals as well as humans.
RSV is a retrovirus that contains two copies of a plus-strand  RNA genome. Its genome consists of four main open...
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Retroviruses

Retroviruses and retrotransposons both insert copies of their genetic elements into the genome of the host cell. Thus, the viral genes are passed on when the host genome is replicated or translated. A typical retroviral DNA sequence contains 3-4 genes that encode the different proteins required for its structural assembly and function as a molecular parasite. This DNA is transcribed into a single mRNA, which is very similar in structure to conventional mRNAs, i.e., it is capped at the 5’...

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Recurrent ZC3H18 mutations stabilize oncogenic endogenous retroviral RNA.

Tanzina Tanu1, Anna M Cox1, Jennifer A Karlow2

  • 1Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02115, USA.

Cell Reports
|June 24, 2026
PubMed
Summary

Mutations in ZC3H18 (Z18) promote cancer by increasing endogenous retroviral (ERV) RNA. This study reveals Z18

Keywords:
CP: cancerCP: molecular biologyERV RNANEXT complexendogenous retroviral RNAmelanomanuclear RNA surveillancenuclear exosome targeting complexzebrafish

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Published on: January 30, 2019

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • Endogenous retroviral (ERV) RNA is highly expressed in various cancers.
  • ZC3H18 (Z18) is a nuclear RNA surveillance factor frequently lost in cancer.

Purpose of the Study:

  • To investigate the role of ZC3H18 mutations in cancer.
  • To determine the impact of ZC3H18 loss on endogenous retroviral RNA expression and oncogenesis.

Main Methods:

  • Identification of ZC3H18 mutations in cancer datasets.
  • Functional studies in zebrafish and human cancer cell lines.
  • Analysis of ERV RNA expression and localization.

Main Results:

  • Recurrent truncating mutations in ZC3H18 were identified in 30% of cancers.
  • Z18 truncating mutations were found to be oncogenic, accelerating melanoma onset in zebrafish.
  • Z18 mutations lead to increased ERV RNA accumulation and cytoplasmic relocalization.
  • ERV RNA expression was essential for Z18 truncation-mediated melanoma development and human melanoma cell growth.

Conclusions:

  • Z18 plays a critical, evolutionarily conserved role in suppressing oncogenic ERV RNA.
  • Z18 mutations drive oncogenesis by dysregulating ERV RNA surveillance.
  • Targeting Z18-regulated ERV RNA presents a potential therapeutic strategy for Z18-mutated cancers.