Sequential expression of long noncoding RNA as mRNA gene expression in specific stages of mouse spermatogenesis

Liang, Meng; Li, Wenqing; Tian, Hui; Hu, Tao; Wang, Lu; Lin, Yeong-Jer; Li, Yulei; Huang, He‐Feng; Sun, Fei

doi:10.1038/srep05966

Cited by 72 publications

(56 citation statements)

References 40 publications

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“…48 Using the same microarray platform with isolated SPCs, a second group also identified transcripts that were differentially expressed between adjacent SPC types of mouse spermatogenesis but did not evaluate the dynamics quantitatively. 49 Moreover, neither study investigated the testis specificity of m/lncRNAs, which is a prominent feature of testicular transcripts. Due to the hybridization involved in the microarray technology, expression data suffer from high noise and low sensitivity.…”

Section: Discussionmentioning

confidence: 99%

Expression dynamics, relationships, and transcriptional regulations of diverse transcripts in mouse spermatogenic cells

et al. 2016

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Among all tissues of the metazoa, the transcritpome of testis displays the highest diversity and specificity. However, its composition and dynamics during spermatogenesis have not been fully understood. Here, we have identified 20,639 message RNAs (mRNAs), 7,168 long non-coding RNAs (lncRNAs) and 15,101 circular RNAs (circRNAs) in mouse spermatogenic cells, and found many of them were specifically expressed in testes. lncRNAs are significantly more testis-specific than mRNAs. At all stages, mRNAs are generally more abundant than lncRNAs, and linear transcripts are more abundant than circRNAs. We showed that the productions of circRNAs and piRNAs were highly regulated instead of random processes. Based on the results of a small-scale functional screening experiment using cultured mouse spermatogonial stem cells, many evolutionarily conserved lncRNAs are likely to play roles in spermatogenesis. Typical classes of transcription factor binding sites are enriched in the promoters of testis-specific m/lncRNA genes. Target genes of CREM and RFX2, 2 key TFs for spermatogenesis, were further validated by using ChIP-chip assays and RNA-seq on RFX2-knockout spermatogenic cells. Our results contribute to the current understanding of the transcriptomic complexity of spermatogenic cells and provide a valuable resource from which many candidate genes may be selected for further functional studies.

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Section: Discussionmentioning

confidence: 99%

Expression dynamics, relationships, and transcriptional regulations of diverse transcripts in mouse spermatogenic cells

et al. 2016

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“…We previously identified that the lncRNA Gm2044 is highly expressed in mouse pachytene spermatocytes and regulates germ cell function by inhibiting Utf1 translation (Hu et al, ; Liang et al, ). The gene annotation database BioGPS (http://biogps.org) shows that Gm2044 is not only highly expressed in testicular tissue, but also in ovarian tissue, which suggests that Gm2044 may be involved in ovarian follicular development (Figure a).…”

Section: Resultsmentioning

confidence: 99%

LncRNA Gm2044 promotes 17β‐estradiol synthesis in mpGCs by acting as miR‐138‐5p sponge

Ren

et al. 2019

Molecular Reproduction Devel

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Long noncoding RNAs (lncRNAs) have been demonstrated to play vital roles in mammalian reproduction. Our previous research revealed that lncRNA Gm2044 is highly expressed in mouse spermatocytes and regulates male germ cell function. The gene annotation database BioGPS shows that Gm2044 is not only highly expressed in testicular tissue but also in ovarian tissue, which suggests that Gm2044 may be involved in female reproductive development. In this study, we confirmed that lncRNA Gm2044 promotes 17β‐estradiol synthesis in mouse pre‐antral follicular granulosa cells (mpGCs). Furthermore, bioinformatics methods, western blot, and the luciferase assay proved that Gm2044 functions as a miR‐138‐5p sponge to inhibit the direct target of miR‐138‐5p, Nr5a1, which enhances 17β‐estradiol synthesis through cyp19a1 activation. Taken together, our results provide an insight into the mechanistic roles of lncRNA Gm2044 for 17β‐estradiol synthesis by acting as competing‐endogenous RNAs to modulate the function of mpGCs. Studying the potential lncRNAs, which regulate estradiol release, will be beneficial for the diagnosis and treatment of steroid hormone‐related disease.

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“…In past few years, there have been many studies on lncRNA profiling during different stages of spermatogenesis (41)(42)(43). It is clear from such studies that the transcriptome levels of lncRNAs are greater than those of mRNAs during spermatogenesis and that the expression of lncRNAs is also dynamically regulated.…”

Section: Discussionmentioning

confidence: 99%

Mrhl Long Noncoding RNA Mediates Meiotic Commitment of Mouse Spermatogonial Cells by Regulating Sox8 Expression

Kataruka

Akhade

Kayyar

et al. 2017

Molecular and Cellular Biology

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Long noncoding RNAs (lncRNAs) are important regulators of various biological processes, including spermatogenesis. Our previous studies have revealed the regulatory loop of mrhl RNA and Wnt signaling, where mrhl RNA negatively regulates Wnt signaling and gets downregulated upon Wnt signaling activation. This downregulation of mrhl RNA is important for the meiotic progression of spermatogonial cells. In our present study, we identified the transcription factor Sox8 as the regulatory link between mrhl RNA expression, Wnt signaling activation, and meiotic progression. In contrast to reports from other groups, we report the expression of Sox8 in germ cells and describe the molecular mechanism of Sox8 regulation by mrhl RNA during differentiation of spermatogonial cells. Binding of mrhl RNA to the Sox8 promoter is accompanied by the assembly of other regulatory factors involving Myc-Max-Mad transcription factors, corepressor Sin3a, and coactivator Pcaf. In the context of Wnt signaling, Sox8 directly regulates the expression of premeiotic and meiotic markers. Prolonged Wnt signaling activation in spermatogonial cells leads to changes in global chromatin architecture and a decrease in levels of stem cell markers.KEYWORDS Myc-Mad-Max, Sin3A, Sox8, Wnt signaling, mrhl RNA T he complexity of the eukaryotic genome has been attributed to its multifaceted regulatory networks. Over recent years, significant advancements in high-throughput analyses of the transcriptome have demonstrated the abundance of transcripts that do not code for proteins (noncoding RNAs [ncRNAs]). These ncRNAs are broadly classified as small and long noncoding RNAs. The small ncRNAs, such as microRNA (miRNA) and small interfering RNA (siRNA), play important roles in transcriptional and posttranscriptional gene regulation, while Piwi-associated RNAs (piRNAs) are involved in transposon regulation (1, 2). Another class is that of the long noncoding RNAs (lncRNAs), which are of various sizes between 200 bp and several kilobases (3). The role of lncRNAs in a plethora of functions, for example, dosage compensation (Xist and roX) (4, 5), genomic imprinting (Air and Kcnq1ot1) (6, 7), pluripotency (Evx1as and Hoxb5/6as) (8), cell differentiation and development (Fendrr, Bvht, Miat, Hotair, etc.) (9), nuclear architecture (NEAT1) (10), chromosome segregation (Concr) (11), immune response (lincRNA-EPS, EGOT) (12, 13), etc., have been characterized. lncRNAs bring about such copious functions by employment of diverse mechanisms such as translational inhibition (lincRNA-p21) (14), mRNA degradation (1/2-sbs RNAs) (15), RNA decoys (Gas5) (16)

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Sequential expression of long noncoding RNA as mRNA gene expression in specific stages of mouse spermatogenesis

Cited by 72 publications

References 40 publications

Expression dynamics, relationships, and transcriptional regulations of diverse transcripts in mouse spermatogenic cells

Expression dynamics, relationships, and transcriptional regulations of diverse transcripts in mouse spermatogenic cells

LncRNA Gm2044 promotes 17β‐estradiol synthesis in mpGCs by acting as miR‐138‐5p sponge

Mrhl Long Noncoding RNA Mediates Meiotic Commitment of Mouse Spermatogonial Cells by Regulating Sox8 Expression

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