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 Table of Contents  
Year : 2017  |  Volume : 1  |  Issue : 1  |  Page : 18-22

Role of Related Regulatory Long Noncoding RNAs on Mammalian Spermatogenesis

1 Department of Clinical Laboratory, State Key Laboratory of Reproductive Medicine, Nanjing Obstetrics and Gynecology Hospital Affiliated to Nanjing Medical University, Nanjing, Jiangsu 210029, China
2 Department of Endocrinology, Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing, Jiangsu 210029, China
3 Department of Andrology, State Key Laboratory of Reproductive Medicine, Nanjing Obstetrics and Gynecology Hospital, Affiliated to Nanjing Medical University, Nanjing, Jiangsu 210029, China
4 Department of Reproduction, State Key Laboratory of Reproductive Medicine, Nanjing Obstetrics and Gynecology Hospital Affiliated to Nanjing Medical University, Nanjing, Jiangsu 210029, China

Date of Web Publication17-Jul-2017

Correspondence Address:
Ling-Juan Gao
Department of Clinical Laboratory, Nanjing Obstetrics and Gynecology Hospital Affiliated to Nanjing Medical University, Nanjing, Jiangsu 210029
Xiu-Feng Ling
Department of Reproduction, State Key Laboratory of Reproductive Medicine, Nanjing Obstetrics and Gynecology Hospital Affiliated to Nanjing Medical University, Nanjing, Jiangsu 210029
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/2096-2924.210690

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Long noncoding RNAs (lncRNAs) are transcribed by RNA molecules, which are longer than 200 nucleotides that lack an open reading frame of significant length and possess no obvious protein-coding capacity. Studies have shown that lncRNAs participate in many physiological processes such as gene imprinting and X chromosome inactivation. They regulate gene expression mainly through DNA methylation, histone modification, and chromatin remodeling. LncRNAs can also affect the development of diseases, and they can be useful to diagnose and treat diseases. With the development of new sequencing and microarray techniques, hundreds of lncRNAs involved in spermatogenesis have been identified, but their functions in the testis are undefined. Herein, we will discuss the biology and regulation of lncRNAs, as well as the bioinformatics tools and searchable databases used to study them in the testis. We hope that this information will provide new insights in treating male reproductive diseases.

Keywords: Epigenetics; Long Noncoding RNA; Long Noncoding RNA Database; Spermatogenesis

How to cite this article:
Liu KS, Mao XD, Pan F, Gao LJ, Ling XF. Role of Related Regulatory Long Noncoding RNAs on Mammalian Spermatogenesis. Reprod Dev Med 2017;1:18-22

How to cite this URL:
Liu KS, Mao XD, Pan F, Gao LJ, Ling XF. Role of Related Regulatory Long Noncoding RNAs on Mammalian Spermatogenesis. Reprod Dev Med [serial online] 2017 [cited 2022 Jan 18];1:18-22. Available from: https://www.repdevmed.org/text.asp?2017/1/1/18/210690

Kang.Sheng Liu and Xiao.Dong Mao contributed equally to this work.

  Introduction Top

Higher organisms transcribe large amounts of RNAs, however, only a fraction of these transcripts encode proteins or polypeptides, which occupy only 2% of the entire genome. The rest transcripts are noncoding RNAs (ncRNAs). Based on the length of the RNA, ncRNAs can be further classified as small noncoding RNAs (sncRNAs, <200 nt) or long noncoding RNAs (lncRNA, >200 nt). NcRNAs, which were long, thought to be transcriptional noise because they lack biological functions.[1] On the other hand, of all the transcripts in the human genome, only 1.2% are mRNAs, and the others are ncRNAs, suggesting that ncRNAs may have important roles in organisms.[2] SncRNAs regulate the expression of target genes at both transcriptional and posttranscriptional levels.[3],[4] LncRNAs are polyadenylated and catalyzed by RNA polymerase II and found in the nucleus and cytoplasm where they possess various biological functions.[5],[6]

According to the World Health Organization survey, 15% of childbearing-age couples are infertile, and in developing countries, it can be 30%. With the aggravation of environmental problems, food safety issues, and electromagnetic radiation, the incidence of infertility is on the rise.[7],[8] Male factors are responsible for half of these cases.[9] Although the assisted reproductive technologies, such as in vitro fertilization and intracytoplasmic sperm injection, have helped some infertile males. However, a larger proportion of male victims, their causes for infertility are still unknown (e.g., nonobstructive azoospermia or nonocclusive azoospermia). This becomes a bottleneck for clinical treatment.[10]

A man produces more than 100 million sperm a day through spermatogenesis. After a complex and precisely regulated process, fertilizable gametes are produced. Although hundreds of genes are turned on and off during spermatogenesis,[11] transcription ceases in round spermatids (RS) and genes are regulated posttranscriptionally by ncRNAs. For example, lncRNAs participate in the proliferation, differentiation, and self-renewal of stem cells, including embryonic stem cells, induced pluripotent stem cells, and spermatogonial stem cells (SSCs). They also play roles in the regulation of the cell cycle, apoptosis, and the inhibition of reproductive system tumors.[12],[13],[14],[15],[16] LncRNAs may be useful biomarkers to detect spermatogenic abnormalities. Herein, we will review the biology and regulation of lncRNAs, as well as highlight the research methods used to study them. Special emphasis will be placed on the functions of lncRNAs in spermatogenesis.

  Classification of LNCRNAs Top

With the introduction of high-throughput sequencing, thousands of lncRNAs have been identified, characterized, and categorized. However, there is no consensus on how they should be categorized.

According to different origins, lncRNAs can be classified into five categories as follows:[17],[18] (i) tandem duplicates in adjacent repeat units; (ii) juxtaposed and restructured lncRNAs in untranscribed and separated gene sequence during chromosome recombination; (iii) duplicates of nonencoding genes in reverse transcription; (iv) lncRNAs produced due to frame fracture of protein-coding genes; and (v) lncRNAs produced by transposable element insertion.

According to its positional relationship with neighboring protein-coding genes, lncRNAs can be classified as follows: (i) antisense lncRNA; (ii) intronic lncRNA; (iii) divergent lncRNA; (iv) intergenic lncRNA; and (v) enhancer lncRNA.

  Lncrna Databases Top

With recent advances in the field of ncRNAs, information on their biological characteristics (e.g., gene organization characteristics, sequence conservation, expression profiles, molecular interactions, epigenetic modifications, and functional annotation) increases with time. At present, few investigators have established lncRNA information databases, which provide basic information on lncRNAs (e.g., primary sequence and genome seat). One of these databases, the deep Base database, integrates the analytical process of lncRNA identification based on the RNA-seq data set, thereby providing lncRNA expression profile data from 478 data sets of 14 species, predicting functions, and analyzing the evolutionary conservation of these lncRNAs (http://biocenter.sysu.edu. Cn/deep Base/index. php).[19] The DIANA-LncBase database is a collection of experimental evidence and miRNA-lncRNA target relationships predicted by the DIANA-micro T algorithm.[20] The ChIP-Base database provides information on how transcription factors regulate lncRNAs and miRNAs (http://deepbase.sysu.edu.cn/chipbase/index.php).[21] The lncRNA database is a relatively professional database to date, including comprehensive annotation of lncRNAs in eukaryotic organisms (http://www.lncrnadb.org/).[22] LncRNADisease is a Chinese database of lncRNAs and human diseases, containing data of multiple lncRNAs and their relevance to human diseases.[23] LNCipedia provides the primary sequence and secondary structure of human lncRNAs and evaluates the protein transcriptional potential of lncRNA with bioinformatic tools and ribosome sequencing data.[24] LncRNASNP also includes information on single-nucleotide polymorphisms in human and mouse lncRNAs, data from the genome-wide association study (GWAS), and their impact on lncRNA structure and lncRNA-miRNA combination.[25] LncR Nome is developed by the Indian Institution of CSIR Genome and Integrative Biology. It provides stable annotations, cross-references, and biologically relevant information and resources that support biological significance of lncRNAs and integrate it into the comprehensive knowledge base.[26]

NONCODE organizes the full-scale information of lncRNAs in 16 species, including the location, sequence, expression profile, evolutionary conservation, functional annotation, and relevant diseases.[27] A microRNA target database, supported by high-throughput experimental data (CLIP-Seq, aka, PAR-CLIP, and iCLIP) and mRNA degradome sequencing data, describes the regulatory relationships between micro RNA (miRNA) and mRNA, miRNA and lncRNA, miRNA and circRNA, miRNA and ceRNA, and RNA and protein. This database integrates and constructs intersections and regulatory relationships among multiple popular target prediction platforms and establishes the ceRNA regulatory network to predict lncRNA functions.[28] LncRNAtor collects data from TC-GA, GEO, ENCODE, and mod ENCODE, and compiles lncRNA expression profiles for cancer samples, as well as provides protein-coding gene co-expression analysis and gene ontology (GO) enrichment analysis of co-expressed genes.[29] It provides information on the differential expression of lncRNAs, identifies tissue or cellular expression with specific microarray, and confirms the results by qPCR. The interference and overexpression of RNA can be used to study specific lncRNA functions.

  Function of Lncrnas in Spermatogenesis Top

Function of long noncoding RNAs

LncRNAs are by-products of Pol II transcription and long thought to be transcriptional noise with no biological function.[30],[31] However, more and more studies indicated that lncRNAs were not the “dark matter” of the genome, and lncRNAs were found to be involved in DNA methylation or demethylation, RNA interference, histone modification, and chromatin remodeling in spermatogenesis and fertilization.[32],[33],[34],[35],[36],[37],[38] Some lncRNAs are precursors of some functional sn-cRNAs (e.g., miRNAs, siRNAs, and piwiRNAs) that indirectly regulate target genes.[38]

LncRNAs possess spatial- and temporal-specific expressions,[39] and they execute their biological functions as follows:[6] (i) recruit chromatin to modify related enzymes, and direct the protein complex to the regulatory sites in cis- or trans-orientation (as guide molecules), (ii) bind directly with transcription factors and proteins to block their actions on target genes, regulating target gene transcription indirectly (as bait molecules), (iii) regulate target genes by identifying the key transcription factors in various signaling pathways (as signaling molecules), and (iv) recruit proteins to form ribonucleoprotein complexes, thereby regulating target genes at the epigenetic level through histone modification (as scaffold molecules).

Unlike mRNAs, lncRNAs are not conserved in primary sequence, except that promoter region and splicing site is conserved.[40] This feature endows lncRNAs with highly conserved secondary and tertiary structures, which are crucial to their biological functions.

Genetic and epigenetic mechanisms are involved in gene expression during, as well as after, transcription. DNA methylation, a key epigenetic modification, plays a critical role in spermatogenesis.[41] A recent study suggested that the expression of lncRNAs is dynamically regulated on the development of male germ cells. Analyzed by ArrayStar on mouse lncRNA, the expression of lncRNAs and mRNAs at six time points (E12.5, E15.5, P7, P14, P21, and adult) was evaluated. They also found that the high level of lncRNAs was closely correlated with the expression level of adjacent mRNAs (<30 kb).[42]

In 2013, results from a study of Sun et al.[43] represented the first systematic investigation of lncRNA expression in the mammalian testis. They employed microarray technology to examine lncRNA expression profiles of neonatal (6-day-old) and adult (8-week-old) mouse testes. They found that 8,265 lncRNAs were expressed above background levels during postnatal testis development, of which 3,025 were differentially expressed. Candidate lncRNAs were identified for further characterization by an integrated examination of genomic context, GO enrichment of their associated protein-coding genes, promoter analysis for epigenetic modification, and evolutionary conservation of elements. Many lncRNAs overlapped or were adjacent to key transcription factors and other genes involved in spermatogenesis. Most differentially expressed lncRNAs exhibited epigenetic modification marks similar to protein-coding genes and tend to be expressed in a tissue-specific manner. In addition, the majority of differentially expressed lncRNAs harbored evolutionary conserved elements.

In 2014, results from a study of Liang et al.[44] suggested that the sequential expression of lncRNA as mRNA gene expression exhibits coordinated changes in male spermatogenesis. They profiled the expression of lncRNAs and mRNAs in each type of germ cells (SSCs, type A spermatogonia [A], pachytene spermatocytes [PS], and RS) by microarray analysis. They analyzed the total expression of lncRNA/mRNA in these four germ cells and found that the maximum number of lncRNAs expression is in A (22,127), and the minimum is in PS (14,456). In addition, the maximum number of mRNAs is in A (19,923), and the minimum is in PS (13,941). Furthermore, the trend in the number of specific lncRNAs was similar to the number of specific mRNAs in each type of germ cells (e.g., maximum in A and minimum in PS). The trend in the number of lncRNAs was similar to the number of mRNAs in two continued types of germ cells (e.g., maximum in SSC to A and minimum in PS to RS).

LncRNA Neat1, Malat1, Mrh1, HongrES2, narcolepsy candidate-region 1 gene expression in spermatogenesis

SSCs differentiate into sperm through spermatogenesis, which involves various genes such as Bcl6b, Etv5, Kit L, and EPCAM. Neat1, a 3.2 kb lncRNA, participates in the formation of paraspeckles structure. Neat1, along with other protein-RNA complex, also participates in the modification of genes' transcription. In 2012, Nakagawa et al.[45] found that Malat1 (a type of lncRNA) was embedded in the subnuclei of cells, and with pre-mRNA regulates many biological processes, such as the growth of synapses and change of cellular cycles. In 2014, An et al.[37] found that Neat1 was expressed in rat testicular tissues and GC-l cell lines. After the injection of lentiviruses, testicular indexes in the experimental group rose, but not significantly. At the same time, the proportion of seminiferous tubules harboring sperms dropped to 86%, indicating that Neat1 regulated rat spermatogenesis.

With a length of 2.4 kb, Mrhl is a type of single-axon lncRNA encoded by the nuclear genome and expressed in testes.[46] In 2008, Ganesan and Rao [47] found that Mrhl can regulate spermatogenesis through two molecular mechanisms. First, Mrhl is divided by Drosha into a midbody of 80 nt. These RNAs are located in the nuclei of GC1 spermatogonial lines, probably interacting with chromatin. Second, Wnt is critical to mammalian spermatogenesis.[48] Cooperating with p68, Mrhl shows its negative regulation in Wnt signal. Knockdown Mrhl expression in GC-1 SPg cell line can disrupt the expression of genes that are responsible for cell signal transduction and development. Most of these genes are members of the Wnt signaling pathway which known to promote cell differentiation and inhibit cell growth. Therefore, Mrhl is crucial for spermatogonial division and differentiation.[49] Further studies are needed in gene knockout mice to define the function and regulation of Mrhl in spermatogenesis.

Male infertility is often caused by maturation arrest (MA). HongrES2 is a 1,588-nt lncRNA co-transcribed by rats' chromosome 5 and 9 and expressed in testis; its expression increases at the end of the first round of spermatogenesis. Space-time specificity of this expression is manifested in the spermatogenesis. Mil-HongrES2, the spliced HongrES2, can downregulate the expression of CES7, the products of which show an important role in capacitation.[50] Interestingly, nuclei weakly express mil-HongrES2, but strongly express HongrES2, indicating that an unknown splicing mechanism exists. Therefore, HongrES2 can regulate the maturating process of sperms.[49] Besides, the overexpression of mil-HongrES2 can weaken spermatic capacitation, indicating the contribution of lowly expressed endogenic HongrES2 to spermatic development.[51]

Narcolepsy candidate-region 1 gene (NLC1-C) is cytoplasmic lncRNA expressed in spermatogonia and early spermatocytes. NLC1-C overexpression promotes cell growth, whereas its loss inhibits cell growth and accelerates apoptosis. Microarray analysis indicated NLC1-C was lower expressed in MA patients than normal person. In another study, NLC1-C was reported to bind to the RNA-binding domain of nucleolin, which inhibited the transcription of miR-320a and miR-383 and induced the proliferation of spermatogonia and early spermatocytes in MA patients.[52]

LncRNAs fine-tune the global genes expression

With the development of high-throughput sequencing, it was found that “dark matters” in eukaryotic genomes were highly and specifically expressed lncRNA in testicular tissues. This expression is an important phenomenon in spermatogenesis. Using the CRISPR system, Wen et al.[53] reported that 1/3 loss of lncRNA could disorder spermatogenesis in Drosophila. Knocked-out lncRNAs of some Drosophila could be repaired with translocation, suggesting the transfunction of lncRNAs. According to gene expression profile, most functional lncRNAs participate in the global genes expression during spermatogenesis. According to relative evolution analysis, lncRNAs evolve faster than encoding genes. The more functions lncRNAs have, the more sequence conservation they show. Different from the switch of encoding genes, lncRNAs regulate the global expression through fine-tune, indicating their promoting role in spermatogenesis.[53]

  Results and Future Perspectives Top

More and more lncRNAs were reported that they participated in spermatogenesis, including cell growth and cell differentiation. Unlike miRNAs, lncRNAs are less conservative. The function of lncRNA should be further studied. Nonconservative lncRNAs have overlapped functional domains. LncRNAs have various functions with various factors, such as decoy molecules, guide molecules, and scaffold molecules. All these molecules are engaged in the expression. As a form of epigenetic regulation, lncRNAs may function in reproductive processes (like spermatogenesis) through histone modification and chromatin reconstruction. Different expressions of lncRNA, Neat1, Mrhl, and HongrES2 build up a regulating network in spermatogenesis, providing us a new perspective to look into the essence of male reproduction. Besides, lncRNAs regulate the global expression through fine-tune, indicating their promoting role in spermatogenesis.

Further studies are needed to understand the roles of lncRNAs in spermatogenesis. With the rapid development of new technologies and searchable databases, such as bioinformatic tools and ontology databases, lncRNAs may serve as biomarks and/or targets to diagnose and/or treat male infertility in future.

Financial support and sponsorship


Conflicts of interest

There are no conflicts of interest.

  References Top

Wapinski O, Chang HY. Long noncoding RNAs and human disease. Trends Cell Biol 2011;21:354-61. doi: 10.1016/j.tcb.2011.04.001.  Back to cited text no. 1
Ponting CP, Belgard TG. Transcribed dark matter: Meaning or myth? Hum Mol Genet 2010;19:R162-8. doi: 10.1093/hmg/ddq362.  Back to cited text no. 2
Li L, Liu Y. Diverse small non-coding RNAs in RNA interference pathways. Methods Mol Biol 2011;764:169-82. doi: 10.1007/978-1-61779-188-8_11.  Back to cited text no. 3
Simon SA, Meyers BC. Small RNA-mediated epigenetic modifications in plants. Curr Opin Plant Biol 2011;14:148-55. doi: 10.1016/j.pbi.2010.11.007.  Back to cited text no. 4
Okamura K. Diversity of animal small RNA pathways and their biological utility. Wiley Interdiscip Rev RNA 2012;3:351-68. doi: 10.1002/wrna.113.  Back to cited text no. 5
Wang KC, Chang HY. Molecular mechanisms of long non-coding RNAs. Mol Cell 2011;43:904-14. doi: 10.1016/j.molcel.2011.08.018.  Back to cited text no. 6
Rhi J, Ben-haroush A. Distribution of causes of infertility in patients attending primary fertility clinics in Israel. Isr Med Assoc J 2011;13:51-4.  Back to cited text no. 7
Nieschlag EH, Nieschlag S. Andrology: Male Reproductive Health and Dysfunction. Berlin: Springer; 2010.  Back to cited text no. 8
Jungwirth A, Giwercman A, Tournaye H, Diemer T, Kopa Z, Dohle G, et al. European Association of urology guidelines on male infertility: The 2012 update. Eur Urol 2012;62:324-32. doi: 10.1016/j.eururo.2012.04.048.  Back to cited text no. 9
Haddad FH, Omari AA, Malkawi OM, Ajour WK, Izat A, Khasrof H, et al. Patterns of testicular cytology in men with primary infertility: Any change since the Gulf War? Acta Cytol 2004;48:807-12. doi: 1128/AEM.00772-09.  Back to cited text no. 10
Holt JE, Stanger SJ, Nixon B, McLaughlin EA. Non-coding RNA in spermatogenesis and epididymal maturation. Adv Exp Med Biol 2016;886:95-120. doi: 10.1007/978-94-017-7417-8_6.  Back to cited text no. 11
Cheng EC, Lin H. Repressing the repressor: A lincRNA as a MicroRNA sponge in embryonic stem cell self-renewal. Dev Cell 2013;25:1-2. doi: 10.1016/j.devcel.2013.03.020.  Back to cited text no. 12
Conte F, Fiscon G, Chiara M, Colombo T, Farina L, Paci P. Role of the long non-coding RNA PVT1 in the dysregulation of the ceRNA-ceRNA network in human breast cancer. PLoS One 2017;12:e0171661. doi: 10.1371/journal.pone.0171661.  Back to cited text no. 13
Zhang X, Gao F, Fu J, Zhang P, Wang Y, Zeng X. Systematic identification and characterization of long non-coding RNAs in mouse mature sperm. PLoS One 2017;12:e0173402. doi: 10.1371/journal.pone.0173402.  Back to cited text no. 14
Kogo R, Shimamura T, Mimori K, Kawahara K, Imoto S, Sudo T, et al. Long noncoding RNA HOTAIR regulates polycomb-dependent chromatin modification and is associated with poor prognosis in colorectal cancers. Cancer Res 2011;71:6320-6. doi: 10.1158/0008-5472.CAN-11-1021.  Back to cited text no. 15
Qu B, Gu Y, Shen J, Qin J, Bao J, Hu Y, et al. Trehalose maintains vitality of mouse epididymal epithelial cells and mediates gene transfer. PLoS One 2014;9:e92483. doi: 10.1371/journal.pone.0092483.  Back to cited text no. 16
Gong C, Maquat LE. lncRNAs transactivate STAU1-mediated mRNA decay by duplexing with 3' UTRs via Alu elements. Nature 2011;470:284-8. doi: 10.1038/nature09701.  Back to cited text no. 17
Ponting CP, Oliver PL, Reik W. Evolution and functions of long noncoding RNAs. Cell 2009;136:629-41. doi: 10.1016/j.cell. 2009.02.006.  Back to cited text no. 18
Zheng LL, Li JH, Wu J, Sun WJ, Liu S, Wang ZL, et al. Deep base v2.0: Identification, expression, evolution and function of small RNAs, lncRNAs and circular RNAs from deep-sequencing data. Nucleic Acids Res 2016;44:D196-202. doi: 10.1093/nar/gkv1273.  Back to cited text no. 19
Paraskevopoulou MD, Vlachos IS, Karagkouni D, Georgakilas G, Kanellos I, Vergoulis T, et al. DIANA-LncBase v2: Indexing microRNA targets on non-coding transcripts. Nucleic Acids Res 2016;44:D231-8. doi: 10.1093/nar/gkv1270.  Back to cited text no. 20
Yang JH, Li JH, Jiang S, Zhou H, Qu LH. ChIPBase: A database for decoding the transcriptional regulation of long non-coding RNA and microRNA genes from ChIP-Seq data. Nucleic Acids Res 2013;41:D177-87. doi: 10.1093/nar/gks1060.  Back to cited text no. 21
Quek XC, Thomson DW, Maag JL, Bartonicek N, Signal B, Clark MB, et al. lncRNAdb v2.0: Expanding the reference database for functional long noncoding RNAs. Nucleic Acids Res 2015;43:D168-73. doi: 10.1093/nar/gku988.  Back to cited text no. 22
Chen G, Wang Z, Wang D, Qiu C, Liu M, Chen X, et al. LncRNADisease: A database for long-non-coding RNA-associated diseases. Nucleic Acids Res 2013;41:D983-6. doi: 10.1093/nar/gks1099.  Back to cited text no. 23
Volders PJ, Helsens K, Wang X, Menten B, Martens L, Gevaert K, et al. LNCipedia: A database for annotated human lncRNA transcript sequences and structures. Nucleic Acids Res 2013;41:D246-51. doi: 10.1093/nar/gks915.  Back to cited text no. 24
Gong J, Liu W, Zhang J, Miao X, Guo AY. lncRNASNP: A database of SNPs in lncRNAs and their potential functions in human and mouse. Nucleic Acids Res 2015;43:D181-6. doi: 10.1093/nar/gku1000.  Back to cited text no. 25
Bhartiya D, Pal K, Ghosh S, Kapoor S, Jalali S, Panwar B, et al. lncRNome: A comprehensive knowledgebase of human long noncoding RNAs. Database (Oxford) 2013;2013:bat034. doi: 10.1093/database/bat034.  Back to cited text no. 26
Zhao Y, Li H, Fang S, Kang Y, Wu W, Hao Y, et al. NONCODE 2016: An informative and valuable data source of long non-coding RNAs. Nucleic Acids Res 2016;44:D203-8. doi: 10.1093/nar/gkv1252.  Back to cited text no. 27
Li JH, Liu S, Zhou H, Qu LH, Yang JH. Star base v2.0: Decoding miRNA-ceRNA, miRNA-ncRNA and protein – RNA interaction networks from large-scale CLIP-Seq data. Nucleic Acids Res 2014;42:D92-7. doi: 10.1093/nar/gkt1248.  Back to cited text no. 28
Park C, Yu N, Choi I, Kim W, Lee S. lncRNAtor: A comprehensive resource for functional investigation of long non-coding RNAs. Bioinformatics 2014;30:2480-5. doi: 10.1093/bioinformatics/btu325.  Back to cited text no. 29
St. Laurent G, Wahlestedt C, Kapranov P. The landscape of long noncoding RNA classification. Trends Genet 2015;31:239-51. doi: 10.1016/j.tig.2015.03.007.  Back to cited text no. 30
Mercer TR, Mattick JS. Structure and function of long noncoding RNAs in epigenetic regulation. Nat Struct Mol Biol 2013;20:300-7. doi: 10.1038/nsmb.2480.  Back to cited text no. 31
Bai Y, Dai X, Harrison AP, Chen M. RNA regulatory networks in animals and plants: A long noncoding RNA perspective. Brief Funct Genomics 2015;14:91-101. doi: 10.1093/bfgp/elu017.  Back to cited text no. 32
Wierzbicki AT. The role of long non-coding RNA in transcriptional gene silencing. Curr Opin Plant Biol 2012;15:517-22. doi: 10.1016/j.pbi.2012.08.008.  Back to cited text no. 33
Kanduri C. Kcnq1ot1: A chromatin regulatory RNA. Semin Cell Dev Biol 2011;22:343-50. doi: 10.1016/j.semcdb.2011.02.020.  Back to cited text no. 34
Rinn JL, Chang HY. Genome regulation by long noncoding RNAs. Annu Rev Biochem 2012;81:145-66. doi: 10.1146/annurev-biochem-051410-092902.  Back to cited text no. 35
Guil S, Esteller M. Cis-acting noncoding RNAs: Friends and foes. Nat Struct Mol Biol 2012;19:1068-75. doi: 10.1038/nsmb.2428.  Back to cited text no. 36
An J, Zhang X, Qin J, Wan Y, Hu Y, Liu T, et al. The histone methyltransferase ESET is required for the survival of spermatogonial stem/progenitor cells in mice. Cell Death Dis 2014;5:e1196. doi: 10.1038/cddis.2014.171.  Back to cited text no. 37
Ma X, Shao C, Jin Y, Wang H, Meng Y. Long non-coding RNAs: A novel endogenous source for the generation of dicer-like1-dependent small RNAs in Arabidopsis thaliana. RNA Biol 2014;11:373-90. doi: 10.4161/rna.28725.  Back to cited text no. 38
Zhu J, Fu H, Wu Y, Zheng X. Function of lncRNAs and approaches to lncRNA-protein interactions. Sci China Life Sci 2013;56:876-85. doi: 10.1007/s11427-013-4553-6.  Back to cited text no. 39
Johnsson P, Lipovich L, Grandér D, Morris KV. Evolutionary conservation of long non-coding RNAs; sequence, structure, function. Biochim Biophys Acta 2014;1840:1063-71. doi: 10.1016/j.bbagen. 2013.10.035.  Back to cited text no. 40
Shen C, Zhong N. Long non-coding RNAs: The epigenetic regulators involved in the pathogenesis of reproductive disorder. Am J Reprod Immunol 2015;73:95-108. doi: 10.1111/aji.12315.  Back to cited text no. 41
Bao J, Wu J, Schuster AS, Hennig GW, Yan W. Expression profiling reveals developmentally regulated lncRNA repertoire in the mouse male germline. Biol Reprod 2013;89:107. doi: 10.1095/biolreprod. 113.113308.  Back to cited text no. 42
Sun J, Lin Y, Wu J. Long non-coding RNA expression profiling of mouse testis during postnatal development. PLoS One 2013;8:e75750. doi: 10.1371/journal.pone.0075750.  Back to cited text no. 43
Liang M, Li W, Tian H, Hu T, Wang L, Lin Y, et al. Sequential expression of long noncoding RNA as mRNA gene expression in specific stages of mouse spermatogenesis. Sci Rep 2014;4:5966. doi: 10.1038/srep05966.  Back to cited text no. 44
Nakagawa S, Ip JY, Shioi G, Tripathi V, Zong X, Hirose T, et al. Malat1 is not an essential component of nuclear speckles in mice. RNA 2012;18:1487-99. doi: 10.1261/rna.033217.112.  Back to cited text no. 45
Nishant KT, Ravishankar H, Rao MR. Characterization of a mouse recombination hot spot locus encoding a novel non-protein-coding RNA. Mol Cell Biol 2004;24:5620-34. doi:10.1128/MCB.24.12.5620-5634.2004.  Back to cited text no. 46
Ganesan G, Rao SM. A novel noncoding RNA processed by Drosha is restricted to nucleus in mouse. RNA 2008;14:1399-410. doi: 10.1261/rna.838308.  Back to cited text no. 47
Kerr GE, Young JC, Horvay K, Abud HE, Loveland KL. Regulated Wnt/beta-catenin signaling sustains adult spermatogenesis in mice. Biol Reprod 2014;90:3. doi: 10.1095/biolreprod.112.105809.  Back to cited text no. 48
Yeh JR, Zhang X, Nagano MC. Wnt5a is a cell-extrinsic factor that supports self-renewal of mouse spermatogonial stem cells. J Cell Sci 2011;124(Pt 14):2357-66. doi: 10.1242/jcs.080903.  Back to cited text no. 49
Zhang L, Liu Q, Zhou Y, Zhang Y. Baculo-expression and enzymatic characterization of CES7 esterase. Acta Biochim Biophys Sin (Shanghai) 2009;41:731-6. doi: 10.1093/abbs/gmp061.  Back to cited text no. 50
Ni MJ, Hu ZH, Liu Q, Liu MF, Lu MH, Zhang JS, et al. Identification and characterization of a novel non-coding RNA involved in sperm maturation. PLoS One 2011;6:e26053. doi: 10.1371/journal.pone.0026053.  Back to cited text no. 51
Lü M, Tian H, Cao YX, He X, Chen L, Song X, et al. Downregulation of miR-320a/383-sponge-like long non-coding RNA NLC1-C (narcolepsy candidate-region 1 genes) is associated with male infertility and promotes testicular embryonal carcinoma cell proliferation. Cell Death Dis 2015;6:e1960. doi: 10.1038/cddis.2015.267.  Back to cited text no. 52
Wen K, Yang L, Gao G, Di C, Ma D, Wu M, et al. Critical roles of long noncoding RNAs in Drosophila spermatogenesis. Genome Res 2016;26:1233-44.  Back to cited text no. 53


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Lncrna Databases
Function of Lncr...
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