Molecular insight into the mammalian SLFN14 ribonuclease

SLFN14 is an endoribonuclease and post-transcriptional regulator that targets the ribosome and its associated RNA substrates for codon-bias translational repression. SLFN14 nuclease activity is functionally linked to antiviral defense, megakaryocyte maturation, and platelet function. Dysregulation of SLFN14 results in human diseases, such as ribosomopathies and bleeding disorders, thus underscoring the importance of establishing the molecular signals coordinating its RNA processing activity. Despite its role in gene regulation and disease, the molecular basis for SLFN14 substrate recognition and catalytic activation remains unclear.