A Testis-Specific Long Noncoding RNA, Start, Is a Regulator of Steroidogenesis in Mouse Leydig Cells

Otsuka, Kai; Matsubara, Shin; Shiraishi, Akira; Takei, Natsumi; Satoh, Yui; Terao, Miho; Takada, Shuji; Kotani, Tomoya; Satake, Honoo; Kimura, Atsushi

doi:10.3389/fendo.2021.665874

Cited by 20 publications

(14 citation statements)

References 107 publications

(133 reference statements)

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“…Start , an lncRNA at this locus, is expressed in both Leydig cells and germ cells. In our previous study, we verified that Start regulates the production of testosterone via activation of two steroidogenic genes, Star and Hsd3b1 , in Leydig cells [ 30 ]. Localization of Start in the cytosol of Leydig cells led to the presumption that the steroidogenic genes are regulated at the posttranscriptional level by Start .…”

Section: Introductionmentioning

confidence: 84%

“…The experimental procedures used in this study were approved by the Institutional Animal Use and Care Committee at Hokkaido University. Start -KO mice were generated as previously described [ 30 ]. The mice were maintained on 14 hr light/10 hr dark cycles at 25℃ and given food and water ad libitum.…”

Section: Methodsmentioning

confidence: 99%

“…Localization of Start in the cytosol of Leydig cells led to the presumption that the steroidogenic genes are regulated at the posttranscriptional level by Start . In contrast, in pachytene spermatocytes, Start is localized in the nucleus [ 30 ]. These results suggest that Start functions at the transcriptional level.…”

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: Introductionmentioning

confidence: 84%

Section: Methodsmentioning

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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“…Start (steroidogenesis activating lncRNA in testis) is a lncRNA with a regulatory role in the testis. It is Leydig specific and may regulate steroidogenesis [Otsuka et al, 2021]. CRISPR/Cas9-generated Start knockout (KO) mice showed an increased expression of genes involved in steroidogenesis, such as Star and Hsd3b1, as demonstrated by RNA-seq and RT-qPCR.…”

Section: Steroidogenesismentioning

confidence: 99%

Non-Coding RNAs: lncRNAs, miRNAs, and piRNAs in Sexual Development

Burgos

Hurtado

Jiménez

et al. 2021

Sex Dev

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Non-coding RNAs (ncRNAs) are a group of RNAs that do not encode functional proteins, including long non-coding RNAs (lncRNAs), microRNAs (miRNAs), PIWI-interacting RNAs (piRNAs), and short interfering RNAs (siRNAs). In the last 2 decades an effort has been made to uncover the role of ncRNAs during development and disease, and nowadays it is clear that these molecules have a regulatory function in many of the developmental and physiological processes where they have been studied. In this review, we provide an overview of the role of ncRNAs during gonad determination and development, focusing mainly on mammals, although we also provide information from other species, in particular when there is not much information on the function of particular types of ncRNAs during mammalian sexual development.

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“…Indeed, lncRNAs were proved to take part in spermatogenesis by deleting hundreds of testicular-specific lncRNAs in the non-mammal drosophila [ 8 ]. Kai Otsuka et al found that lncRNA Start transcripted at Prss/Tessp sites acted on Leydig cells to fine-tune steroid production pathways subtly in the testis in mice [ 9 ]. Another testicular germ cell-specific lncRNA, Teshl, preferentially regulated gene expression of the Y chromosome and maintained progeny sex ratio [ 10 ].…”

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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A Testis-Specific Long Noncoding RNA, Start, Is a Regulator of Steroidogenesis in Mouse Leydig Cells

Cited by 20 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

Non-Coding RNAs: lncRNAs, miRNAs, and piRNAs in Sexual Development

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

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