Ribosomal protein S6 phospho-deficient mice display altered novelty-induced locomotion, synaptic plasticity, and specific mRNA translation

By high-throughput RNA-seq of heavy polysomal fractions, we report that rpS6 knockin mice, in which the 5 phosphorylatable serines have been replaced by alanines, show an alteration in the translation, but not transcription, of a subset of mRNAs in the nucleus accumbens (NAc) but not in the dorsal striatum (DStr). Gene Ontology analysis revealed that multiple dysregulated mRNAs are related to the mitochondria. Moreover, we described that rpS6 knockin mice also display an alteration in novelty-induced locomotion and synaptic plasticity. mRNAs from heavy polysomal fractions (Heavy) and total RNA (Total) from both the nucleus accumbens (Nac) and dorsal striatum (DStr) were compared between rpS6 knockin mice and wildtype littermates. We sequenced triplicates per genotype and brain region.通过对重度多聚核糖体组分开展高通量RNA测序，我们报道了rpS6敲入小鼠（rpS6 knockin mice）——其5个可磷酸化丝氨酸残基已被丙氨酸替换——在伏隔核（nucleus accumbens，NAc）而非背侧纹状体（dorsal striatum，DStr）中，出现特定mRNA子集的翻译水平异常，但转录水平未受影响。基因本体（Gene Ontology，GO）分析显示，多份异常调控的mRNA与线粒体功能相关。此外，我们还发现rpS6敲入小鼠存在新奇刺激诱导的运动能力与突触可塑性异常。我们对rpS6敲入小鼠与野生型同窝仔鼠的伏隔核、背侧纹状体中，重度多聚核糖体组分的mRNA（Heavy）以及总RNA（Total）进行了对比分析，每个基因型与脑区均设置三份生物学重复并完成测序。