miR-137 is a highly conserved microRNA (miRNA) that is associated with the control of brain function and the etiology of psychiatric disorders including schizophrenia and bipolar disorder. The Caenorhabditis elegans genome encodes a single miR-137 ortholog called mir-234, the function of which is unknown. Here we show that mir-234 is expressed in a subset of sensory, motor and interneurons in C. elegans. Using a mir-234 deletion strain, we systematically examined the development and function of these neurons in addition to global C. elegans behaviors. We were however unable to detect phenotypes associated with loss of mir-234, possibly due to genetic redundancy. To circumvent this issue, we overexpressed mir-234 in mir-234-expressing neurons to uncover possible phenotypes. We found that mir-234-overexpression endows resistance to the acetylcholinesterase inhibitor aldicarb, suggesting modification of neuromuscular junction (NMJ) function. Further analysis revealed that mir-234 controls neuropeptide levels, therefore positing a cause of NMJ dysfunction. Together, our data suggest that mir-234 functions to control the expression of target genes that are important for neuropeptide maturation and/or transport in C. elegans. SIGNIFICANCE STATEMENT: The miR-137 family of miRNAs is linked to the control of brain function in humans. Defective regulation of miR-137 is associated with psychiatric disorders that include schizophrenia and bipolar disorder. Previous studies have revealed that miR-137 is required for the development of dendrites and for controlling the release of fast-acting neurotransmitters. Here, we analyzed the function a miR-137 family member (called mir-234) in the nematode animal model using anatomical, behavioral, electrophysiological and neuropeptide analysis. We reveal for the first time that mir-234/miR-137 is required for the release of slow-acting neuropeptides, which may also be of relevance for controlling human brain function.

中文翻译：

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mir-234控制秀丽隐杆线虫神经肌肉接头处的神经肽释放。

miR-137是高度保守的microRNA（miRNA），与大脑功能的控制以及包括精神分裂症和躁郁症在内的精神疾病的病因有关。秀丽隐杆线虫基因组编码称为mir-234的单个miR-137直向同源物，其功能未知。在这里，我们显示mir-234在秀丽隐杆线虫的感觉，运动和中间神经元的子集中表达。使用mir-234缺失株，我们系统地检查了这些神经元的发育和功能以及全球秀丽隐杆线虫的行为。但是，我们可能无法检测到与mir-234缺失相关的表型，这可能是由于基因冗余所致。为了规避此问题，我们在表达mir-234的神经元中过度表达了mir-234，以发现可能的表型。我们发现，mir-234过表达赋予了对乙酰胆碱酯酶抑制剂涕灭威的抗性，表明神经肌肉接头（NMJ）功能的修改。进一步的分析表明，mir-234控制神经肽水平，因此是NMJ功能障碍的原因。在一起，我们的数据表明，mir-234的功能是控制靶基因的表达，这对于秀丽隐杆线虫的神经肽成熟和/或运输很重要。意义声明：miR-137家族的miRNA与人类大脑功能的控制有关。miR-137的调控缺陷与精神病相关，包括精神分裂症和双相情感障碍。先前的研究表明，miR-137是树突发育和控制速效神经递质释放所必需的。这里，我们使用解剖，行为，电生理和神经肽分析方法分析了线虫动物模型中miR-137家族成员（称为mir-234）的功能。我们首次揭示了缓释神经肽的释放需要mir-234 / miR-137，这也可能与控制人脑功能有关。