Dynamic post-transcriptional regulation by Mrn1 links cell wall homeostasis to mitochondrial structure and function

The RNA-binding protein Mrn1 in Saccharomyces cerevisiae targets over 300 messenger RNAs, including many involved in cell wall biogenesis. The impact of Mrn1 on these target transcripts is not known, however, nor is the cellular role for this regulation. We have shown that Mrn1 represses target mRNAs through the action of its disordered, asparagine-rich amino-terminus. Its endogenous targets include the paralogous SUN domain proteins Nca3 and Uth1, which affect mitochondrial structure and function as well as the cell wall, as well as other nuclear-encoded mitochondrial proteins. While loss of MRN1 has no effect on fermentative growth, we found that mrn1Δ yeast adapt more quickly to respiratory conditions. These cells also have enlarged mitochondria in fermentative conditions, an observation that may explain their faster switch to respiration. Our analyses indicated that Mrn1 acts as a hub for integrating cell wall integrity and mitochondrial biosynthesis in a carbon-source responsive manner.酿酒酵母(Saccharomyces cerevisiae)中的RNA结合蛋白(RNA-binding protein) Mrn1可靶向超过300种信使RNA(messenger RNA)，其中诸多参与细胞壁生物发生过程。然而，目前尚不清楚Mrn1对这些靶转录本的调控效应，也未明确该调控的细胞生理功能。本研究证实，Mrn1可通过其固有无序且富含天冬酰胺的氨基末端(amino-terminus)对靶mRNA产生转录后抑制作用。其内源靶标包含旁系同源的SUN结构域蛋白(SUN domain protein) Nca3与Uth1——二者可调控线粒体结构与功能，同时参与细胞壁相关生物学过程——以及其他核编码线粒体蛋白(nuclear-encoded mitochondrial proteins)。尽管MRN1基因缺失对酵母的发酵生长无显著影响，但本研究发现mrn1Δ缺失突变酵母可更快适应呼吸培养条件。该突变菌株在发酵培养条件下还存在线粒体体积增大的表型，这一观测结果或可解释其更快转向呼吸代谢的分子机制。本研究分析表明，Mrn1可作为调控枢纽，以碳源响应的方式整合细胞壁完整性与线粒体生物合成两大生物学过程。