The C-terminal tail of the RBR E3 ligase RNF14 defines branched K6/K48 polyubiquitin specificity in ribosomal quality control.

RNF14’s unstructured C-terminal tail specifies branched K6/K48 polyubiquitin chain formation in vitro and on eRF1 in human cells, defining RQC-linked ubiquitin specificity.

• Why it matters: Branched ubiquitin signals expand the ubiquitin code, but few E3 ligases are known to generate specific branched linkages that function in ribosomal quality control.
• What they did: The authors reconstituted RNF14 ubiquitination in vitro, tested ubiquitination on eRF1 in human cells, and used structural/mechanistic analyses compared with yeast Itt1 to map how the C-terminal tail controls chain type and branching.
• The result: RNF14 forms branched K6/K48 polyubiquitin on eRF1, placing this rare branched linkage into RQC pathways and enabling new studies of branched ubiquitin function.

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