ELAVating insight into Hox RNA processing

Hox genes play a crucial role in assigning cellular identities along the anterior-posterior axis of animal bodies. Hox gene expression can be regulated via transcriptional mechanisms and recent studies have also uncovered a regulatory role for Hox RNA processing, yet the mechanisms underlying this regulation remain unknown. Now, Claudio Alonso and colleagues identify the neural RNA-binding protein ELAV as a key regulator of Hox RNA processing in the Drosophila embryonic central nervous system (p. 2046). The researchers use the Drosophila Hox gene Ultrabithorax (Ubx) as a gene model for investigating RNA processing and discover that elav mutants produce patterns of Ubx alternative splicing and polyadenylation that are distinct from those observed in wild-type embryos. They further demonstrate that ELAV binds directly to discrete elements within Ubx RNA. In the absence of elav, they report, Ubx mRNA and protein levels are reduced, whereas nascent Ubx RNA transcripts accumulate, suggesting that ELAV-dependent processing of Ubx RNA is able to fine-tune the levels of Ubx expressed. Furthermore, an analysis of the cellular pathways affected in elav mutants reveals a role for ELAV in Hox-dependent apoptosis. The authors thus propose a model in which ELAV modulates Hox RNA processing, expression and function in order to regulate local programmes of neural differentiation.