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全基因组和 Poly(A)+转录组分析认知功能障碍突变体。

Whole-Genome and Poly(A)+Transcriptome Analysis of the Mutant with Cognitive Dysfunctions.

机构信息

Pavlov Institute of Physiology, Russian Academy of Sciences, 199034 Saint Petersburg, Russia.

Saint-Petersburg Pasteur Institute, 197101 Saint Petersburg, Russia.

出版信息

Int J Mol Sci. 2024 Sep 13;25(18):9891. doi: 10.3390/ijms25189891.

Abstract

The temperature-sensitive mutant exhibits the restoration of learning defects both after heat shock (HS) and under hypomagnetic conditions (HMC). Previously, was shown to have an increased level of LIM kinase 1 (LIMK1). However, its sequence did not significantly differ from that of the wild-type strain (). Here, we performed whole-genome and poly(A)-enriched transcriptome sequencing of and males normally, after HMC, and after HS. Several high-effect -specific mutations were identified, including (regulation of HS-dependent transcription) and , the human orthologs of which are associated with intellectual disorders. Pronounced interstrain differences between the transcription profiles were revealed. Mainly, they included the genes of defense and stress response, long non-coding RNAs, and transposons. After HS, the differences between the transcriptomes became less pronounced. In , was the only gene whose expression changed after both HS and HMC. The normal downregulation of and in was confirmed by RT-PCR. Analysis of expression did not reveal any interstrain differences or changes after stress. Thus, behavioral differences between CS and both under normal and stressed conditions are not due to differences in transcription. Instead, , and are more likely to contribute to the phenotype.

摘要

温度敏感型突变体在热休克(HS)和低磁条件(HMC)后都表现出学习缺陷的恢复。先前,已经显示出 LIM 激酶 1(LIMK1)的水平增加。然而,其序列与野生型菌株 ()没有显著差异。在这里,我们对正常的 和 雄性、HMC 后和 HS 后进行了全基因组和多聚 A 富集转录组测序。鉴定出了几个高效应 - 特异性突变,包括 (HS 依赖性转录的调节)和 ,其人类同源物与智力障碍有关。揭示了菌株间转录谱之间的明显差异。主要包括防御和应激反应基因、长非编码 RNA 和转座子。HS 后,转录组之间的差异变得不那么明显。在 中,只有 在 HS 和 HMC 后表达发生变化。通过 RT-PCR 证实了 和 在 中的正常下调。对 表达的分析未显示出任何菌株间差异或应激后的变化。因此,CS 和 在正常和应激条件下的行为差异不是由于 转录的差异造成的。相反, 、 和 更有可能导致 表型。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ba77/11432035/4aa5788f1107/ijms-25-09891-g001.jpg

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