Systematic screen of RNA binding proteins that enhance circular RNA translation.

A cell-based screen identified 68 RNA binding proteins as putative activators that enhance noncanonical translation of translatable circular RNAs (circRNAs) driven by IRES-like elements.

• Why it matters: circRNA translation depends on IRES or IRES-like elements, and trans-acting RNA binding proteins that boost this process are not well mapped, limiting engineered RNA synthetic biology.
• What they did: The authors built a cell system to screen RBPs for increased circRNA translation, then used a machine learning algorithm to learn shared sequence features and predict additional candidate activators.
• The result: Validations showed the newly identified and predicted activators promote IRES-mediated circRNA translation in a context-dependent fashion, expanding the set of IRES-related trans-acting factors and engineered RBP tools.

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