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Species-specific KRAB-ZFPs function as repressors of retroviruses by targeting PBS regions.

ABSTRACT: SignificanceHosts often target the relatively conserved regions in rapidly mutating retroviruses to inhibit their replication. One of these regions is called a primer binding site (PBS), which has to be complementary to the host tRNA to initiate reverse transcription. By analyzing endogenous retroviral elements, we found that host cells use this sequence as a target in efforts to block the expression of viral elements. A specific type of zinc finger protein targets the PBS in a host genome, which not only inhibits the transcription of endogenous viruses but also inhibits the replication of exogenous retroviruses with the same PBS. Thus, our study sheds light on a strategy for searching for host restriction factors targeting retroviruses.

SUBMITTER: Yang B

PROVIDER: S-EPMC8931336 | biostudies-literature | 2022 Mar

REPOSITORIES: biostudies-literature

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Species-specific KRAB-ZFPs function as repressors of retroviruses by targeting PBS regions.

Yang Bo B Fang Lu L Gao Qianqian Q Xu Ce C Xu Junqin J Chen Zhen-Xia ZX Wang Yixuan Y Yang Peng P

Proceedings of the National Academy of Sciences of the United States of America 20220308 11

Eukaryotic genomes harbor sequences derived from the chromosomal integration of ancient viruses, such as endogenous retroviruses (ERVs), which comprise 8% of the human genome. Like exogenous retroviruses, ERVs retain many common functional elements, including the corresponding DNA sequences of transfer RNA (tRNA) primer binding sites (PBSs), which are utilized for reverse transcription initiation by exogenous retroviruses. Here, through a medium-scale analysis of PBS loci positioned within ERVs, ...[more]

PMID: 35259018

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