Study shows heterogeneity in ribosomal proteins impacts translation

Immunofluorescence image showing co-expression of paralogues eRpL22 (red) and eRpL22-like (green) in the maturing germline of the Drosophila testis. Credit: M.G. Kearse.
Immunofluorescence image showing co-expression of paralogues eRpL22 (red) and eRpL22-like (green) in the maturing germline of the Drosophila testis. Credit: M.G. Kearse.

A new study from Lehigh University provides further support to the “specialized ribosome” hypothesis by showing for the first time that specialized ribosomal protein paralogues in Drosophila carry out different tasks during spermatogenesis.

“Specialized eRpL22 paralogue-specific ribosomes regulate specific mRNA translation in spermatogenesis in Drosophila melanogaster,” was published in the August 1, 2019, issue of Molecular Biology of the Cell. Authors Vassie C. Ware, professor of molecular biology at Lehigh University, and Catherine M. Mageeney, her former graduate student, found evidence that contradicts the textbook assertion that ribosomes “indiscriminately synthesize proteins in all cells by translating genetic information encoded in messenger RNAs,” Ware said,

“Maria Barna’s laboratory at Stanford University has shown changes in core ribosomal protein content of ribosomes can impact the types of proteins that the ribosome will actually make within stem cells derived from mouse embryos,” said Ware, whose study shows this happening in spermatogenesis in fruit flies.

“Our work is the first to show specialized ribosomes at work in a multicellular organism (the fruit fly) within a differentiation process (spermatogenesis),” said Ware. Previous studies showed that the ribosomal protein paralogues eRpL22 and eRpL22-like (found only in eukaryotic cells) impact lifespan and fertility of the animal, so Ware’s lab honed in on these components for its study.

“We used a technique that allowed us to purify each ribosome type from cells of the fly testis and then to determine what mRNAs were found in association with each ribosome type using RNA sequencing,” Ware said. “Experiments revealed distinct subpopulations of mRNAs are associated with eRpL22 or eRpL22-like ribosomes for over 50% of the RNAs captured from ribosomes. The mRNAs, known to be important for specific stages of spermatogenesis, were found in association with either eRpL22 or eRpL22-like ribosomes.”

“[A]ll ribosomes are not alike!”

Ware’s laboratory also conducted in vitro studies of model testis mRNAs in an engineered fly cell culture system. “Specific association with eRpL22-like ribosomes can occur outside of the testis environment,” they concluded, “thus enabling us to establish an experimental system for testing factors that allow specific mRNAs to be associated with specific ribosome types. Collectively, our results support the hypothesis that paralogue functions are distinguished in spermatogenesis by selective translation of mRNAs required for specific stages of sperm maturation. Indeed, all ribosomes are not alike!” Ware concluded.

It is still unknown how paralogue-specific ribosomes in the male germline target specific mRNAs, she added.

“Our preliminary experiments using an engineered fly cell culture system have proven useful in eliminating ‘germline-specific factors’ as necessary for targeting ‘model’ mRNAs to eRpL22-like ribosomes, since enrichment is recapitulated in the cell system,” said Ware. “We are using our engineered fly cell culture system to explore features of both mRNAs and paralogue-specific ribosomes themselves that govern targeted translation. Additionally, we will use this system to identify ribosome-associated proteins that may be required for the targeting mechanism.”

These findings contribute to understanding the role specialized ribosomes may play in several human disorders of ribosome function called ribosomopathies. “Malfunction of specialized ribosomes may account for how several of these disorders manifest in specific types of cells,” Ware said. “More specifically our work on specialized ribosomes in fruit fly spermatogenesis has implications for understanding factors regulating human sperm development and fertility.”

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Mary Spiro is ASCB's Science Writer and Social Media Manager.