View Program - 63rd Annual Drosophila Research Conference

The Drosophila melanogaster eRpL22 ribosomal protein family contains two structurally divergent & developmentally essential paralogues: eRpL22 and eRpL22-like - the latter exhibits tissue-specific expression across development; the former is ubiquitously expressed. Multi-tissue co-localization comparison of eRpL22-like and core ribosomal components indicates eRpL22-like may have functional roles both within the ribosome itself and apart from ribosomal processes.

Sequencing of RNAs enriched on eRpL22 and eRpL22-like polysomes in adult testes revealed differential enrichment of mRNAs suggesting that paralogue-specific “specialized ribosomes” translate specific mRNAs. Functional enrichment analysis guided investigation into specific tissues by physiology (where to look) and function (what processes, pathways, and programs function differently in Rp mutants). KEGG pathway analysis revealed transcripts differentially enriched on eRpL22-like polysomes were uniquely implicated in pathways not canonically associated with ribosomal functions, including endocytosis, autophagy, and mTOR signaling. Some pathways were over-represented in both polysome types, but these were derived from unique transcripts.

Transcripts of genes functionally implicated in human disease, given by Human Phenotype Ontology (HPO) term association, were over-represented on eRpL22-like polysomes (961:496 terms). Grouping each term into broad categories revealed HPO terms within the genitourinary, musculoskeletal, and nervous systems, and the brain, eye, head and jaw regions, were most functionally enriched on eRpL22-like polysomes (181:8 terms). We have previously shown differential expression of eRpL22-like protein and specific knock-down phenotypes in several analogous regions in the fly.

Conditional knock-out of eRpL22-like resulted in many morphological defects within the ovary, including disruption of the germline stem cell niche, ectopic rounded follicular epithelium cells, oocytes with dual (bifurcated) nuclei, double-anteriorized eggs, and specific spatiotemporal patterns of cell death & oogenesis arrest. This constellation of phenotypes suggests eRpL22-like has a role in ensuring proper cell polarity in early development and the ovary is a viable system to investigate the cellular and molecular basis of these defects.

Taken together, these data broaden the context for essential roles of eRpL22-like across multiple developmental processes.

Physiological and functional implications of differentially enriched transcripts on eRpL22-family polysomes