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

## TL;DR

This study explores how the RNA-binding protein HOW interacts with RNA in fruit fly sperm cells, revealing new insights into RNA regulation during spermatogenesis.

## Contribution

The study identifies novel RNA targets and binding motifs of the cytoplasmic isoform HOW(S) during early spermatogenesis in Drosophila.

## Key findings

- HOW(S) binds to 121 novel transcripts in germ stem cells and spermatogonia, many involved in signal transduction.
- HOW(S) preferentially binds to (A/G/U)CUAAC motifs in 3’-UTRs and GCG(A/U)G in 5’-UTRs.
- Binding of HOW(S) to CUAAC motifs may regulate mRNA stability and translation in a position- and partner-dependent manner.

## Abstract

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.

Identification and characterization of cytoplasmic STAR protein-RNA interactions in D. melanogaster testis germ stem cells and functional impact of binding, providing new insights into the importance of RNA-protein networks during spermatogenesis.