I made fundamental discoveries regarding the role of the conserved Elav/Hu family RNA binding proteins (RBPs) in generating alternative neural transcriptome. I discovered two major roles of the RBPs as follows. First, Elav/Hu RBPs regulate broad landscape of lengthened 3’ UTRs in neurons. Especially, I reported that all three numbers were capable for conferring globally lengthened 3’ UTRs in S2 cells, also provided striking genetic evidence for the importance of splicing regulation of fne by Elav in controlling neural APA which allele abrogated nuclear Fne accumulation in elav mutants thus enhance the regulatory defects of elav mutants. Second, Elav/Hu RBPs co-determine neural alternative splicing in Drosophila. I found that over ~800 genes are regulating for both inclusion and exclusion of cassette exon splicing in sensitive with Elav/Hu expression in neurons, as well as dozens of genes shift towards distal or proximal 3’ ALE isoform usage in that circumstance. Moreover, we provided evidence that Elav and its characteristic U-rich binding sites are enriched downstream of proximal PAS that are prone to bypass in neurons by CLIP studies and motif analysis.

Related Publications
Lee
et al, Plos Genetics 2021
Wei* and Lee* et al, Molecular Cell 2020
(*, co-first authors)