长链非编码 RNA 在精子发生和男性不育中的作用。
Long non-coding RNAs (lncRNAs) in spermatogenesis and male infertility.
机构信息
Division of Endocrinology, Central Drug Research Institute, Lucknow, UP, India.
出版信息
Reprod Biol Endocrinol. 2020 Oct 30;18(1):103. doi: 10.1186/s12958-020-00660-6.
BACKGROUND
Long non-coding RNAs (lncRNAs) have a size of more than 200 bp and are known to regulate a host of crucial cellular processes like proliferation, differentiation and apoptosis by regulating gene expression. While small noncoding RNAs (ncRNAs) such as miRNAs, siRNAs, Piwi-interacting RNAs have been extensively studied in male germ cell development, the role of lncRNAs in spermatogenesis remains largely unknown.
OBJECTIVE
In this article, we have reviewed the biology and role of lncRNAs in spermatogenesis along with the tools available for data analysis.
RESULTS AND CONCLUSIONS
Till date, three microarray and four RNA-seq studies have been undertaken to identify lncRNAs in mouse testes or germ cells. These studies were done on pre-natal, post-natal, adult testis, and different germ cells to identify lncRNAs regulating spermatogenesis. In case of humans, five RNA-seq studies on different germ cell populations, including two on sperm, were undertaken. We compared three studies on human germ cells to identify common lncRNAs and found 15 lncRNAs (LINC00635, LINC00521, LINC00174, LINC00654, LINC00710, LINC00226, LINC00326, LINC00494, LINC00535, LINC00616, LINC00662, LINC00668, LINC00467, LINC00608, and LINC00658) to show consistent differential expression across these studies. Some of the targets of these lncRNAs included CENPB, FAM98B, GOLGA6 family, RPGR, TPM2, GNB5, KCNQ10T1, TAZ, LIN28A, CDKN2B, CDKN2A, CDKN1A, CDKN1B, CDKN1C, EZH2, SUZ12, VEGFA genes. A lone study on human male infertility identified 9879 differentially expressed lncRNAs with three (lnc32058, lnc09522, and lnc98497) of them showing specific and high expression in immotile sperm in comparison to normal motile sperm. A few lncRNAs (Mrhl, Drm, Spga-lncRNAs, NLC1-C, HongrES2, Tsx, LncRNA-tcam1, Tug1, Tesra, AK015322, Gm2044, and LncRNA033862) have been functionally validated for their roles in spermatogenesis. Apart from rodents and humans, studies on sheep and bull have also identified lncRNAs potentially important for spermatogenesis. A number of these non-coding RNAs are strong candidates for further research on their roles in spermatogenesis.
背景
长链非编码 RNA（lncRNA）的大小超过 200bp，已知通过调节基因表达来调节增殖、分化和凋亡等多种关键细胞过程。虽然微小非编码 RNA（ncRNA），如 miRNA、siRNA、Piwi 相互作用 RNA，已在雄性生殖细胞发育中得到广泛研究，但 lncRNA 在精子发生中的作用仍知之甚少。
目的
本文综述了 lncRNA 在精子发生中的生物学和作用，以及用于数据分析的工具。
结果与结论
迄今为止，已有三项微阵列和四项 RNA-seq 研究旨在鉴定小鼠睾丸或生殖细胞中的 lncRNA。这些研究是在产前、产后、成年睾丸和不同的生殖细胞中进行的，以鉴定调节精子发生的 lncRNA。在人类中，对不同的生殖细胞群进行了五项 RNA-seq 研究，包括两项对精子的研究。我们比较了三项关于人类生殖细胞的研究，以鉴定共同的 lncRNA，并发现了 15 个 lncRNA（LINC00635、LINC00521、LINC00174、LINC00654、LINC00710、LINC00226、LINC00326、LINC00494、LINC00535、LINC00616、LINC00662、LINC00668、LINC00467、LINC00608 和 LINC00658），这些 lncRNA 在这些研究中表现出一致的差异表达。这些 lncRNA 的一些靶标包括 CENPB、FAM98B、GOLGA6 家族、RPGR、TPM2、GNB5、KCNQ10T1、TAZ、LIN28A、CDKN2B、CDKN2A、CDKN1A、CDKN1B、CDKN1C、EZH2、SUZ12、VEGFA 基因。一项关于人类男性不育的单独研究确定了 9879 个差异表达的 lncRNA，其中三个（lnc32058、lnc09522 和 lnc98497）在与正常运动精子相比时，在不动精子中表现出特异性和高表达。一些 lncRNA（Mrhl、Drm、Spga-lncRNAs、NLC1-C、HongrES2、Tsx、LncRNA-tcam1、Tug1、Tesra、AK015322、Gm2044 和 LncRNA033862）已被功能验证其在精子发生中的作用。除了啮齿动物和人类外，绵羊和公牛的研究也鉴定出了对精子发生可能重要的 lncRNA。这些非编码 RNA 中的许多都是进一步研究其在精子发生中作用的重要候选者。
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