Held out wings RNA binding activity in the cytoplasm during early spermatogenesis

Held out wings (HOW) is an RNA-binding protein essential for spermatogenesis in Drosophila melanogaster. HOW is a signal transduction and activation of RNA (STAR) protein, regulating post-transcriptional gene expression. The characteristics of RNA-binding by the conserved short cytoplasmic isoform, HOW(S), are unknown. In vivo RIP-seq identified 121 novel transcripts bound by HOW(S) in germ stem cells and spermatogonia, many with signal transduction functions. (A/G/U)CUAAC motifs were enriched in 3’-UTRs and GCG(A/U)G in 5’-UTRs. HOW binds with high affinity to sites containing CUAAC motifs from lola and hipk mRNAs. The binding of cytoplasmic HOW(S) specifically to CUAAC motifs in 3’-UTRs can result in stabilization or destabilization of mRNAs and translational regulation potentially depending on position of binding, number of sites and interacting partners. This study provides new insight into STAR protein-RNA interactions and functions in spermatogenesis.