Structural and Functional Characterization of a Testicular Long Non-coding RNA (4930463O16Rik) Identified in the Meiotic Arrest of the Mouse Topaz1–/– Testes

Chadourne, Manon; Poumerol, Elodie; Jouneau, Luc; Passet, Bruno; Castille, Johan; Sellem, Eli; Pailhoux, Eric; Mandon‐Pepin, Béatrice

doi:10.3389/fcell.2021.700290

Cited by 7 publications

(8 citation statements)

References 107 publications

(132 reference statements)

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“…Only a few of the many lncRNAs expressed in the testis have been functionally assessed and characterized [47][48][49][50]. Some mouse models with KO of lncRNAs in germ cells showed a defect in meiosis, smaller number of sperm, and less motile sperm, although no phenotype was reported in other KO mice [8][9][10]51]. In Leydig cells, lncRNAs were predicted to regulate the miRNA-mRNA network [20,[52][53][54][55].…”

Section: Plos Onementioning

confidence: 99%

“…These findings suggest biological significance of lncRNAs in the testis. Indeed, knockout (KO) mouse models of several testis-specific lncRNAs showed defects in the production or quality of sperm [8][9][10], and in vivo knockdown of lncRNAs in the testis resulted in obvious impairment of spermatogenesis [11,12]. However, only a few lncRNAs have been functionally assessed.…”

Section: Introductionmentioning

confidence: 99%

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Evidence for a functional role of Start, a long noncoding RNA, in mouse spermatocytes

et al. 2022

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A mouse testis-specific long noncoding RNA (lncRNA), Start, is localized in the cytosol of Leydig cells and in the nucleus of pachytene spermatocytes. We previously showed that Start regulates steroidogenesis through controlling the expression of Star and Hsd3b1 genes in Leydig cells, but its function in germ cells was not known. Here we verified that a spermatocyte-specific protease gene, Prss43/Tessp-3, was downregulated in Start-knockout testes. To investigate the transcriptional regulatory activity of Start in spermatocytes, we first performed a series of reporter gene assays using a thymidine kinase promoter in spermatocyte-derived GC-2spd(ts) cells. A 5.4-kb genome sequence encompassing Start exhibited enhancer activity for this promoter, and the activity was decreased by knockdown of Start. Deletion of the Start promoter and replacement of the Start sequence abolished the enhancer activity and, consistently, the activity was detected in further experiments only when Start was actively transcribed. We then examined whether the Prss43/Tessp-3 gene could be a target of Start. A reporter gene assay demonstrated that the 5.4-kb sequence exhibited enhancer activity for a Prss43/Tessp-3 promoter in GC-2spd(ts) cells and that the activity was significantly decreased by knockdown of Start. These results suggest that Start functions in transcriptional activation of the Prss43/Tessp-3 gene in spermatocytes. Given that Start is presumed to regulate steroidogenic genes at the posttranscriptional level in Leydig cells, the function in spermatocytes is a novel role of Start. These findings provide an insight into multifunctionality of lncRNAs in the testis.

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Section: Plos Onementioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Evidence for a functional role of Start, a long noncoding RNA, in mouse spermatocytes

et al. 2022

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“…In mice, lncRNA 4930463O16Rik is known to be related to the protein expression of Topaz1, a germ cell-specific gene that is highly conserved in mammals. The deletion of TOPAZ1 disrupts the expression of lncRNA 4930463O16Rik and can lead to male infertility [34]. In addition, lncRNAs are highly associated with the maturational process in sperm.…”

Section: Regulation Of Lncrnas In Meiosis and Spermatogenesismentioning

confidence: 99%

“…With the development of high throughput sequencing technology, many functional lncRNAs have been discovered, and many of these lncRNAs are thought to be involved in the formation of spermatozoa [33][34][35][36]. The expression profiles of lncRNAs in germ cells at different developmental stages were identified in mouse testes using gene chips and a large number of differentially expressed lncRNAs (DELs) were detected at different developmental stages [37].…”

Section: Introductionmentioning

confidence: 99%

Long Noncoding RNAs: Recent Insights into Their Role in Male Infertility and Their Potential as Biomarkers and Therapeutic Targets

Zhao

Heng

Sahlu

et al. 2021

IJMS

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Long noncoding RNAs (lncRNAs) are composed of nucleotides located in the nucleus and cytoplasm; these are transcribed by RNA polymerase II and are greater than 200 nt in length. LncRNAs fulfill important functions in a variety of biological processes, including genome imprinting, cell differentiation, apoptosis, stem cell pluripotency, X chromosome inactivation and nuclear transport. As high throughput sequencing technology develops, a substantial number of lncRNAs have been found to be related to a variety of biological processes, such as development of the testes, maintaining the self-renewal and differentiation of spermatogonial stem cells, and regulating spermatocyte meiosis. These indicate that lncRNAs can be used as biomarkers and potential therapeutic targets for male infertility. However, only a few comprehensive reviews have described the role of lncRNAs in male reproduction. In this paper, we summarize recent findings relating to the role of lncRNAs in spermatogenesis, their potential as biomarkers for male infertility and the relationship between reproductive arrest and transgenerational effects. Finally, we suggest specific targets for the treatment of male infertility from the perspective of lncRNAs.

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“…It is a complex differentiation process and involves spermatogonium, spermatocyte, and haploid sperm stages [ 1 , 2 ]. Every step of spermatogenesis is strictly and precisely controlled by many genetic and non-genetic factors [ 3 , 4 ]. It is very important to explore new factors that regulate spermatogenesis to reveal the pathological mechanisms of male infertility.…”

Section: Introductionmentioning

confidence: 99%

lncRNA 1700101O22Rik and NONMMUG030480.1 Are Not Essential for Spermatogenesis in Mice

Zhou

Dong

Chen

et al. 2022

IJMS

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Many testis-specific lncRNAs are highly expressed in late spermatogenesis, especially in spermiogenesis. However, their functions and the underlying mechanisms in male fertility are largely unknown. Here, we screened two highly expressed lncRNAs, 1700101O22Rik (O22Rik) and NONMMUG030480.1 (NM480) in testes, to investigate the roles in spermatogenesis using lncRNA knockout (KO) mouse generated by CRISPER/Cas9 technology. Both testis-specific lncRNAs were mainly expressed from secondary spermatocytes to round spermatids, suggesting that they might be involved in spermiogenesis. Phenotypic analysis showed that the deletion of O22Rik or NM480 did not affect the development of testis and epididymis or spermatogenesis. These results were confirmed in both young and middle-aged male mice. In addition, there was no significant difference in sperm morphology and other parameters including concentration and motility between wild type (WT) and KO mice. Fertility tests showed that litter size was significantly lower in O22Rik KO mice compared with WT controls. Although O22Rik did not exert dramatic roles in spermatogenesis, on molecular levels, its surrounding gene expression was disturbed significantly. Gm32773 was decreased; however, Gm32828 was increased in KO mice. In conclusion, lncRNA O22Rik and NM480 are not individually essential for spermatogenesis in mice.

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Structural and Functional Characterization of a Testicular Long Non-coding RNA (4930463O16Rik) Identified in the Meiotic Arrest of the Mouse Topaz1–/– Testes

Cited by 7 publications

References 107 publications

Evidence for a functional role of Start, a long noncoding RNA, in mouse spermatocytes

Evidence for a functional role of Start, a long noncoding RNA, in mouse spermatocytes

Long Noncoding RNAs: Recent Insights into Their Role in Male Infertility and Their Potential as Biomarkers and Therapeutic Targets

lncRNA 1700101O22Rik and NONMMUG030480.1 Are Not Essential for Spermatogenesis in Mice

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