Autophagy-mediated post-transcriptional surveillance of meiotic translation in Saccharomyces Cerevisiae

ABSTRACT

In Saccharomyces cerevisiae, macroautophagy/autophagy plays a pivotal role and is indispensable for multiple meiotic processes. In this study, we demonstrate that Rim4, a meiosis-specific RNA-binding protein (RBP) that holds back the translation of a specific subset of meiotic transcripts until its programmed degradation by autophagy during meiotic divisions, forms a heterotrimeric complex in vivo with the yeast YWHA/14-3-3 proteins Bmh1 and Bmh2, which effectively expels mRNAs from Rim4’s binding grip. We pinpoint four distinct Bmh1 and Bhm2 binding sites (BBSs) in the Rim4 structure, with two of them nestled within the RNA recognition motifs (RRMs). The phosphorylation states at these BBSs controlled by counteracting PKA and Cdc14 phosphatase activities determine whether Rim4 interacts with Bmh1, Bmh2 or the mRNAs, thereby regulating Rim4’s subcellular distribution, function, and stability for autophagy. Remarkably, we found that Rim4 is an Atg11-dependent selective autophagy substrate and activates Atg1 during meiotic divisions, only after its sequential dissociation from mRNAs and Bmh1 or Bmh2 assisted by PKA and cytosolic Cdc14, respectively. These findings reveal an intricate mechanism that underpins the autophagy-mediated surveillance of Rim4-mRNA interactions, orchestrated by meiotic PKA and Cdc14 activities, to ensure stage-specific translation of key meiotic transcripts.

KEYWORDS:

• Selective autophagy
• meiotic translational control
• Rim4
• Cdc14
• PKA
• 14-3-3 proteins

Acknowledgements

We thank members of the Wang lab for comments on the manuscript. This work was supported by a grant from the National Institutes of Health to F. Wang (R01GM133899) and from the Welch Foundation to F. Wang (I-2019-20190330), as well as funding from Nancy Cain and Jeffrey A. Marcus Scholar in Medical Research, in Honor of Dr. Bill S. Vowell, to F. Wang.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Additional information

Funding

The work was supported by the National Institute of General Medical Sciences [R01GM133899]; Welch Foundation [I-2019-20190330].