Non-coding RNAs and their interaction with RNA-binding proteins regulate mRNA levels in key cellular processes. This has intensified interest in post-transcriptional regulation. Recent studies on the turnover of AU-rich cytokine mRNAs have linked mRNA metabolism with ubiquitination. Ubiquitin is well recognized for its role in protein regulation/degradation. In the present paper, we describe a new group of RNA-binding E3 ubiquitin ligases which are predicted to bind and regulate RNA stability. Although much effort has been focused on understanding the role of these proteins as key regulators of mRNA turnover, the requirement for E3 ligase activity in mRNA decay remains unclear. It is remarkable that the ubiquitin system is involved, either directly or indirectly, in both the degradation of nucleic acids as well as proteins. These new RNA-binding E3 ligases are potential candidates which link two important cellular regulatory pathways: the regulation of both protein and mRNA stability.