Lessenger Alexander T, Skotheim Jan M, Swaffer Mathew P, Feldman Jessica L
Department of Biology, Stanford University, Stanford, CA, USA.
Chan-Zuckerberg Biohub , San Francisco, CA, USA.
J Cell Biol. 2025 Mar 3;224(3). doi: 10.1083/jcb.202403154. Epub 2024 Dec 9.
Cell size and biosynthetic capacity generally increase with increased DNA content. Somatic polyploidy has therefore been proposed to be an adaptive strategy to increase cell size in specialized tissues with high biosynthetic demands. However, if and how DNA concentration limits cellular biosynthesis in vivo is not well understood. Here, we show that polyploidy in the Caenorhabditis elegans intestine is critical for cell growth and yolk biosynthesis, a central role of this organ. Artificially lowering the DNA/cytoplasm ratio by reducing polyploidization in the intestine gave rise to smaller cells with dilute mRNA. Highly expressed transcripts were more sensitive to this mRNA dilution, whereas lowly expressed genes were partially compensated-in part by loading more RNA Polymerase II on the remaining genomes. Polyploidy-deficient animals produced fewer and slower-growing offspring, consistent with reduced synthesis of highly expressed yolk proteins. DNA-dilute cells had normal total protein concentration, which we propose is achieved by increasing the expression of translational machinery at the expense of specialized, cell-type-specific proteins.
细胞大小和生物合成能力通常会随着DNA含量的增加而增加。因此，体细胞多倍体被认为是一种适应性策略，用于在具有高生物合成需求的特化组织中增加细胞大小。然而，DNA浓度在体内是否以及如何限制细胞生物合成，目前尚不清楚。在这里，我们表明秀丽隐杆线虫肠道中的多倍体对于细胞生长和卵黄生物合成至关重要，而卵黄生物合成是该器官的核心作用。通过减少肠道中的多倍化来人为降低DNA/细胞质比率，会产生具有稀释mRNA的较小细胞。高表达的转录本对这种mRNA稀释更敏感，而低表达基因则部分得到补偿——部分是通过在剩余基因组上加载更多的RNA聚合酶II来实现的。多倍体缺陷动物产生的后代数量减少且生长缓慢，这与高表达卵黄蛋白合成减少一致。DNA稀释的细胞具有正常的总蛋白浓度，我们认为这是通过增加翻译机制的表达来实现的，代价是牺牲专门的、细胞类型特异性的蛋白质。
