Rnf10, also known as Ring Finger Protein 10, is an E3 ubiquitin ligase. It plays essential roles in ribosome-associated quality control pathways. Specifically, it monoubiquitinates ribosomal proteins like RPS3, which is crucial for dissociating stalled ribosomes and responding to ribosomal subunit imbalance [1]. It is also involved in the initiation-specific ribosome-associated quality control pathway (iRQC), where it ubiquitylates 40S proteins uS3 and uS5 leading to 40S decay [2]. In addition, Rnf10 is implicated in synaptonuclear signaling in neurons, influencing neuronal morphology [3].

Knockdown of RPS proteins, which disrupts 40S ribosome biogenesis, results in proteasomal degradation of RNF10. Conversely, knockdown of RPL proteins, which impairs 60S biogenesis, leads to the accumulation of stalled initiating 40S subunits, increased RNF10 levels, and RPS3 monoubiquitination [1]. Depleting the critical scanning helicase eIF4A1 impairs 40S ubiquitylation and degradation, indicating mRNA engagement is required for iRQC activation by RNF10 [2]. In macrophages, knockdown of RNF10 enhances both the nuclear factor-κB and interferon regulatory factor 3 signaling pathways, promoting proinflammatory cytokines and type I interferons [4]. In pirarubicin-induced cardiotoxicity models, overexpression of RNF10 antagonizes the cardiotoxicity by regulating the AP-1/Meox2 signaling pathway [5,6].

In summary, Rnf10 is a key regulator in ribosome-related quality control, synaptonuclear signaling, and immune-related pathways. Model-based research, especially knockdown and overexpression studies, has revealed its significance in conditions such as ribosomal subunit imbalance, age-related inflammation, and pirarubicin-induced cardiotoxicity. Understanding Rnf10's functions provides potential therapeutic targets for related diseases.