Autophagy-mediated post-transcriptional surveillance of meiotic translation in Saccharomyces Cerevisiae.
Autophagy-mediated post-transcriptional surveillance of meiotic translation in Saccharomyces Cerevisiae.
复制标题
自噬介导的酿酒酵母减数分裂翻译的转录后监测。
DOI：
10.1080/15548627.2023.2276632
复制
发表时间：
2024
期刊：
影响因子：
13.3
通讯作者：
Wang,Fei
中科院分区：
文献类型：
--
作者：
Zhang,Rudian;Feng,Wenzhi;Qian,Suhong;Wang,Fei
在酿酒酵母中，大自噬/自噬在多个减数分裂过程中起着至关重要的作用。在这项研究中，我们证明了Rim 4，减数分裂特异性RNA结合蛋白（RBP），阻止减数分裂转录的特定子集的翻译，直到其程序化降解的自噬在减数分裂分裂期间，形成异源三聚体复合体在体内与酵母YWHA/14-3-3蛋白Bmh 1和Bmh 2，有效地驱逐mRNA从Rim 4的结合抓地力。我们在Rim 4结构中定位了四个不同的Bmh 1和Bhm 2结合位点（BBS），其中两个位于RNA识别基序（RRM）内。通过抵消PKA和Cdc 14磷酸酶活性控制的这些BBS的磷酸化状态决定了Rim 4是否与Bmh 1，Bmh 2或mRNA相互作用，从而调节Rim 4的亚细胞分布，功能和自噬稳定性。值得注意的是，我们发现Rim 4是Atg 11依赖的选择性自噬底物，并在减数分裂期间激活Atg 1，只有在PKA和胞质Cdc 14分别协助其从mRNA和Bmh 1或Bmh 2中顺序解离后。这些发现揭示了一种复杂的机制，该机制支持自噬介导的Rim 4-mRNA相互作用的监视，由减数分裂PKA和Cdc 14活动协调，以确保关键减数分裂转录物的阶段特异性翻译。
InSaccharomyces 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 complexin vivowith 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.