Mov10 in developing brain suppresses retroelements and regulates neuronal development and function. Mus musculus

RNA helicase MOV10 participates in RNA-induced gene silencing, nonsense-mediated decay and suppression of retrotransposition in cultured cells. We describe a critical role for MOV10 in early postnatal brain, where there is an ~40 fold increase in MOV10 protein levels along with a nucleo-cytoplasmic localization pattern. The isolation of MOV10-associated RNAs from this stage showed a preponderance of retrotransposon encoded RNAs along with messenger RNAs. Furthermore, reduced MOV10 expression led to an increase in genomic L1 levels in P2 brain. We show that MOV10 likely suppresses retrotransposition by binding to the LINE1 reverse transcriptase and blocking cDNA synthesis. MOV10 also binds cytoskeletal mRNAs and is required for normal neurite outgrowth in both Neuro2A and cultured hippocampal neurons. Finally, standard MOV10 levels in brain are required for normal mouse behavior. We provide the first evidence of a role for MOV10 in retrotransposon control in brain and in neuronal development and function. Overall design: The analysis includes 8 samples. The wildtype Neuro2a cells have 2 replicates each of differentiated and undifferentiated cells.The remaining 4 are CRISPR-Cas Knockout lines for MOV10 that are have also been differentiated or left undifferentiated. These samples are also in replicates.

RNA解旋酶（RNA helicase）MOV10可在培养细胞中参与RNA诱导的基因沉默、无义介导的mRNA降解（nonsense-mediated decay）以及逆转录转座（retrotransposition）抑制过程。本研究阐明了MOV10在出生后早期大脑中的关键作用：此时MOV10蛋白水平上调约40倍，且呈现核质共定位（nucleo-cytoplasmic localization pattern）的分布特征。从该阶段脑组织中分离得到的MOV10结合RNA，其主要组分为逆转录转座子编码RNA与信使RNA。此外，MOV10表达下调会导致P2小鼠脑组织中的基因组L1元件水平升高。本研究证实，MOV10可能通过结合长散在核元件1（LINE1）逆转录酶并阻断互补DNA（cDNA）合成，从而抑制逆转录转座。MOV10还可结合细胞骨架信使RNA，且对于Neuro2A细胞与原代培养海马神经元的正常神经突生长不可或缺。最后，大脑中维持正常水平的MOV10表达对于小鼠的正常行为表现至关重要。本研究首次证实了MOV10在大脑内逆转录转座子调控、神经元发育与功能中的作用。整体实验设计：本分析共包含8个样本。野生型Neuro2A细胞分为分化组与未分化组，每组各设2个生物学重复；剩余4个样本为MOV10的CRISPR-Cas敲除（CRISPR-Cas Knockout）细胞系，同样分为分化组与未分化组，且均设置生物学重复。