Phage anti-CRISPR control by an RNA- and DNA-binding helix–turn–helix protein

The approximately 40 kDa Aca2-RNA complex reveals how the HTH domain simultaneously binds DNA and RNA to regulate anti-CRISPR gene expression.

• HTH domain proteins are crucial for adjusting gene expression in response to cellular needs.
• Aca2 represses anti-CRISPR gene production by binding to DNA and inhibiting mRNA translation.
• Binding to conserved RNA stem-loops prevents ribosome access, further regulating protein synthesis.
• The structure of the Aca2-RNA complex illustrates the selective binding of the HTH domain to RNA versus DNA.
• These regulatory mechanisms are common within the Aca2 family, suggesting a broader role for HTH proteins in gene expression control.

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