Autophagy inspects Rim4-mRNA interaction to safeguard programmed meiotic translation

Autophagy can degrade RNA, with an intricate preference for specific RNAs. However, the mechanism remains unclear. During yeast meiosis, autophagy is active, while a subset of transcripts needs to survive until their programmed translation during and at the end of meiotic divisions. Thus, the challenge here is how meiotic autophagy temporally spares specific mRNAs. Rim4, a meiosis-specific RNA binding protein (RBP), sequesters a specific set of mid-late meiotic transcripts during early meiosis to suppress premature translation. Recently, we reported that autophagy degrades Rim4, while the underlying mechanism and the fate of transcripts in complex with Rim4 remain uncharacterized. Here, we show that Rim4 utilizes a nuclear localization signal (NLS) to enter the nucleus to load its mRNA substrates before the nuclear export. Once in the cytoplasm, the active autophagy spares Rim4-mRNA. Using combined genetic, biochemical, and cell imaging approaches, we show that autophagy selectively degrades Rim4 during meiotic divisions in an Atg11-dependent manner upon Rim4-bound mRNAs released for translation; meanwhile, released mRNAs also become sensitive to autophagy. In vitro, purified Rim4 and its RRM-motif-containing variants, but not Rim4-mRNA complex, activate Atg1 kinase activity in meiotic cell lysates and in the immunoprecipitated Atg1 complex, suggesting that the conserved RRMs are involved in stimulating Atg1 and hence selective autophagy. These findings indicate that autophagy inspects Rim4-mRNA interaction to ensure meiotic stage-specific translation.