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主管单位 工业和信息化部 主办单位 哈尔滨工业大学 主编 任南琪 国际刊号ISSN 1672-5565 国内刊号CN 23-1513/Q

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引用本文:宋逸钒,倪挺,魏刚.小鼠精子发生中环形RNA生成和功能分析[J].生物信息学,2020,18(1):22-30.
SONG Yifan,NI Ting,WEI Gang.Biogenesis and function analysis on circular RNAs in mouse spermatogenesis[J].Chinese Journal of Bioinformatics,2020,18(1):22-30.
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小鼠精子发生中环形RNA生成和功能分析
宋逸钒,倪挺,魏刚
(复旦大学 生命科学学院,上海 200438)
摘要:
小鼠精子发生过程中存在大量环状RNA(circRNA,circular RNA),其来源和功能尚不清楚。利用生物信息学手段分析小鼠精子发生过程中5个时期(精原干细胞,原始精原细胞、前细线期精母细胞,粗线期精母细胞及圆形精子细胞)的circRNA,共发现3万余个circRNA。对circRNA两侧内含子中的重复序列分析发现:circRNA两侧内含子中显著富集反向互补重复序列。这些重复序列不仅包括已报道的SINE/Alu序列,还包括SINE/B2、SINE/B4、LINE/L1,LTR/ERVL-MaLR和LTR/ERVK,暗示多种类别的反向互补序列有可能参与了精子发生过程中的circRNA形成。采用sailfish-cir和maSigPro对获得的circRNA进一步定量和差异表达分析,发现5个不同时期的精子细胞中共存在409个差异表达circRNA,它们所在基因能够富集在与精子发生密切相关的功能类群上。对差异表达的circRNA进行miRNA结合预测,共发现有137个circRNA-miRNA结合位点。精子发生相关基因来源的circRNA序列中有93%含有与翻译有关的m6A基序,暗示精子发生进程中的部分circRNA有形成多肽的潜力。研究发现小鼠精子发生过程中许多circRNA具有RNA结合蛋白(RBP)结合位点,提示circRNA可能具有“RBP海绵”的潜在功能。
关键词:  精子发生  circRNA  反向重复序列  RBP海绵
DOI:10.12113/201906005
分类号:R318.04
文献标识码:A
基金项目:国家重点研发计划项目(No.2018YFC1003500).
Biogenesis and function analysis on circular RNAs in mouse spermatogenesis
SONG Yifan, NI Ting, WEI Gang
(School of Life Sciences, Fudan University, Shanghai 200438, China)
Abstract:
HJ1.7mm]Large amounts of circRNAs (circular RNA) exist in mouse spermatogenesis. However, their deriving sources and functions are unclear. The present study adopted bioinformatical methods to analyze circRNA in five stages of spermatogenesis (spermatogonial stem cells, primitive type A spermatogonia, preleptotene spermatocytes, pachytene spermatocytes, and round spermatids), and identified over 30 000 circRNAs. Sequence analysis revealed the enrichment of reverse complementary repeated sequences in the flanking introns of circRNAs, including not only the reported SINE/Alu sequences, but also SINE/B2, SINE /B4, LINE/L1, LTR/ERVL-MaLR, and LTR/ERVK, suggested that multiple classes of reverse complement sequences might be involved in circRNA formation during spermatogenesis. Quantitative analysis and differential expression analysis using sailfish-cir and maSigPro revealed 409 differentially expressed circRNAs in sperm cells of five development stages, and their deriving genes were enriched in functional categories closely related to spermatogenesis. Further analysis revealed that 137 potential circRNA-miRNA interactions existed in differentially expressed circRNA. Moreover, 93% of the circRNA sequences derived from the spermatogenesis-related genes contained translation-related m6A motifs, indicating their potential to generate polypeptides. Besides, it was found that many circRNAs had predicted binding site of RNA binding proteins (RBPs), strongly suggesting that circRNA could also have the potential to serve as “RBP sponge”, in addition to its known role of miRNA sponge.
Key words:  Spermatogenesis  circRNA  Reverse repeated sequence  RBP sponge

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