A translation control module coordinates germline stem cell differentiation with ribosome biogenesis duringDrosophilaoogenesis

Abstract

Ribosomal defects perturb stem cell differentiation, causing diseases called ribosomopathies. How ribosome levels control stem cell differentiation is not fully known. Here, we discovered three RNA helicases are required for ribosome biogenesis and for Drosophila oogenesis. Loss of these helicases, which we named Aramis, Athos and Porthos, lead to aberrant stabilization of p53, cell cycle arrest and stalled GSC differentiation. Unexpectedly, Aramis is required for efficient translation of a cohort of mRNAs containing a 5′-Terminal-Oligo-Pyrimidine (TOP)-motif, including mRNAs that encode ribosomal proteins and a conserved p53 inhibitor, Novel Nucleolar protein 1 (Non1). The TOP-motif co-regulates the translation of growth-related mRNAs in mammals. As in mammals, the La-related protein co-regulates the translation of TOP-motif containing RNAs during Drosophila oogenesis. Thus, a previously unappreciated TOP-motif in Drosophila responds to reduced ribosome biogenesis to co-regulate the translation of ribosomal proteins and a p53 repressor, thus coupling ribosome biogenesis to GSC differentiation.

H/ACA snRNP–dependent ribosome biogenesis regulates translation of polyglutamine proteins

“…This hypothesis predicts that compromised ribosome biogenesis will phenocopy loss of H/ACA snRNP complex components. We impaired ribosome biogenesis by depleting ribosomal protein paralogs RpS10b and RpS19b in the germline, as the depletion of other ribosomal proteins that do not have paralogs results in GSC differentiation defects or loss of cyst stages that would mask the cyst differentiation block ( 6 , 39 , 43 , 44 ). Depletion of RpS10b and RpS19b phenocopied loss of H/ACA snRNP complex components, leading to a block in cyst differentiation and decreased levels of Rbfox1 and Bru1 proteins without a concomitant loss of their mRNAs (figs.…”

Pseudouridine-dependent ribosome biogenesis regulates translation of polyglutamine proteins during Drosophila oogenesis

“…This hypothesis predicts that compromised ribosome biogenesis will phenocopy loss of H/ACA box components. We impaired ribosome biogenesis by depleting ribosomal protein paralogs RpS10b and RpS19b in the germline, as the depletion of other ribosomal proteins that do not have paralogs results in GSC differentiation defects or loss of cyst stages that would mask the cyst differentiation block (Jang et al, 2021; Martin et al, 2021; McCarthy et al, 2022; Sanchez et al, 2016). Depletion of RpS10b and RpS19b phenocopied loss of H/ACA box components, leading to a block in cyst differentiation and decreased levels of Rbfox1 and Bru1 proteins without a concomitant loss of their mRNAs ( Figure S7A-S7K, S8A-S8H ).…”