Two miRNA clusters,
            <i>miR-34b/c</i>
            and
            <i>miR-449</i>
            , are essential for normal brain development, motile ciliogenesis, and spermatogenesis

Wu, Jingwen; Bao, Jianqiang; Kim, Min Kyung; Yuan, Shuiqiao; Tang, Chong; Zheng, Huili; Mastick, Grant S.; Xu, Chen; Yan, Wei

doi:10.1073/pnas.1407777111

Cited by 251 publications

(280 citation statements)

References 31 publications

Supporting

Mentioning

259

Contrasting

Order By: Relevance

“…These findings suggest that miRNAs necessary to confer spermatogonial differentiation may be synthesized by non-canonical enzymes, and the underlying mechanism remains to be elucidated. It has recently been found that miR-449 is predominantly expressed in mouse testes and it is mainly located in spermatocytes and spermatids (Bao et al 2012, Wu et al 2014. Interestingly, miR-34b and miR-34c have been found to resemble the 'seed' sequence of miR-449.…”

Section: Functions Of Mirnas In Meiosis and Spermiogenesismentioning

confidence: 99%

“…Interestingly, miR-34b and miR-34c have been found to resemble the 'seed' sequence of miR-449. Coincidentally, miR-34b and miR-34c exhibit a similar effect to that of miR-449 during the development of male germ cells and spermatogenesis (Bouhallier et al 2010, Bao et al 2012, Wu et al 2014. Individual deficiency in miR-34b/c or miR-449 appears to have no obvious effect; however, simultaneous inactivation of miR-34b/34c and miR-449 leads to mouse oligoasthenoteratozoospermia (Wu et al 2014), implicating that double or triple knockout approach of miRNAs is needed to obtain the phenotype for certain miRNAs.…”

Section: Functions Of Mirnas In Meiosis and Spermiogenesismentioning

confidence: 99%

See 1 more Smart Citation

MicroRNAs and DNA methylation as epigenetic regulators of mitosis, meiosis and spermiogenesis

Yao¹,

Liu²,

Sun³

et al. 2015

Reproduction

View full text Add to dashboard Cite

Spermatogenesis is composed of three distinctive phases, which include self-renewal of spermatogonia via mitosis, spermatocytes undergoing meiosis I/II and post-meiotic development of haploid spermatids via spermiogenesis. Spermatogenesis also involves condensation of chromatin in the spermatid head before transformation of spermatids to spermatozoa. Epigenetic regulation refers to changes of heritably cellular and physiological traits not caused by modifications in the DNA sequences of the chromatin such as mutations. Major advances have been made in the epigenetic regulation of spermatogenesis. In this review, we address the roles and mechanisms of epigenetic regulators, with a focus on the role of microRNAs and DNA methylation during mitosis, meiosis and spermiogenesis. We also highlight issues that deserve attention for further investigation on the epigenetic regulation of spermatogenesis. More importantly, a thorough understanding of the epigenetic regulation in spermatogenesis will provide insightful information into the etiology of some unexplained infertility, offering new approaches for the treatment of male infertility.Reproduction (2015) 150 R25-R34

show abstract

Section: Functions Of Mirnas In Meiosis and Spermiogenesismentioning

confidence: 99%

Section: Functions Of Mirnas In Meiosis and Spermiogenesismentioning

confidence: 99%

MicroRNAs and DNA methylation as epigenetic regulators of mitosis, meiosis and spermiogenesis

Yao¹,

Liu²,

Sun³

et al. 2015

Reproduction

View full text Add to dashboard Cite

show abstract

“…The target miRNAs, miR-34b-5p and miR-449a in the testis, which were associated with spermatogenesis or EGME induced-testicular toxicity (Fukushima et al, 2011;Lizé et al, 2011;Smorag et al, 2012;Wu et al, 2014), were applied to RT-qPCR with 7900HT Fast Real Time PCR System (Applied Biosystems). The primers for miR-34b-5p and miR-449a (Assay IDs: #000427 and 001030) were designed based on each respective human sequence obtained from miRBase (http://microrna.sanger.…”

Section: Reverse Transcription-quantitative Real-time Pcr (Rt-qpcr) Amentioning

confidence: 99%

“…Conditional knockout mice that lack dicer, a prerequisite for the production of miRNA, in Sertoli cells are infertile, suggesting the importance of miRNAs on spermatogenesis (Papaioannou et al, 2009). Additionally, several miRNAs such as miR-34b-5p and miR-449a that are preferentially expressed in the testis are assumed to have an intimate involvement in germ cell development (Fukushima et al, 2011;Wu et al, 2014). Indeed, double KO mice with miR-34b/c and miR-449 deficiency had severely disrupted spermatogenesis (Wu et al, 2014).…”

Section: Introductionmentioning

confidence: 99%

“…Additionally, several miRNAs such as miR-34b-5p and miR-449a that are preferentially expressed in the testis are assumed to have an intimate involvement in germ cell development (Fukushima et al, 2011;Wu et al, 2014). Indeed, double KO mice with miR-34b/c and miR-449 deficiency had severely disrupted spermatogenesis (Wu et al, 2014). Moreover, rats treated with EGME had decreases in the levels of several testicular miRNAs including miR449a in line with up-regulation of Bcl-2, which is one of the main target mRNAs of miR-449a (Fukushima et al, 2011).…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

MicroRNA profling in ethylene glycol monomethyl ether-induced monkey testicular toxicity model

et al. 2015

View full text Add to dashboard Cite

-To establish and characterize ethylene glycol monomethyl ether (EGME)-induced testicular toxicity model in cynomolgus monkeys, EGME at 0 or 300 mg/kg was administered orally to sexually mature male cynomolgus monkeys (n = 3/group) for 4 consecutive days. Circulating and testicular micro-RNA (miRNA) profiles in this model were investigated using miRNA microarray or real-time quantitative reverse transcription-PCR methods. EGME at 300 mg/kg induced testicular toxicity in all the monkeys, which was characterized histopathologically by decreases in pachytene spermatocytes and round spermatids, without any severe changes in general conditions or clinical pathology. In microarray analysis, 16 down-regulated and 347 up-regulated miRNAs were detected in the testis, and 326 down-regulated but no up-regulated miRNAs were detected in plasma. Interestingly, miR-1228 and miR-2861 were identified as abundant miRNAs in plasma and the testis of control animals, associated presumably with apoptosis and cell differentiation, respectively, and were prominently increased in the testis of EGME-treated animals, reflecting the recovery from EGME-induced testicular damages via stimulating cell proliferation and differentiation of sperm. Furthermore, down-regulation of miR-34b-5p and miR-449a, which are enriched in meiotic cells like pachytene spermatocytes, was obvious in the testis, suggesting that these spermatogenic cells were damaged by the EGME treatment. In conclusion, EGME-induced testicular toxicity in cynomolgus monkeys was shown, and this model would be useful for investigating the mechanism of EGME-induced testicular toxicity and identifying testicular biomarkers. Additionally, testicular miR-34b-5p and miR-449a were suggested to be involved in damage of pachytene spermatocytes.

show abstract

Characterizing isomiR variants within the microRNA‐34/449 family

et al. 2017

View full text Add to dashboard Cite

miR‐34/449 microRNAs are conserved regulators of multiciliated cell differentiation. Here, we evidence and characterize expression of two isomiR variant sequences from the miR‐34/449 family in human airway epithelial cells. These isomiRs differ from their canonical counterparts miR‐34b and miR‐449c by one supplemental uridine at their 5′‐end, leading to a one‐base shift in their seed region. Overexpression of canonical miR‐34/449 or 5′‐isomiR‐34/449 induces distinct gene expression profiles and biological effects. However, some target transcripts and functional activities are shared by both canonical microRNAs and isomiRs. Indeed, both repress important targets that result in cell cycle blockage and Notch pathway inhibition. Our findings suggest that 5′‐isomiR‐34/449 may represent additional mechanisms by which miR‐34/449 family finely controls several pathways to drive multiciliogenesis.

show abstract

Two miRNA clusters, miR-34b/c and miR-449 , are essential for normal brain development, motile ciliogenesis, and spermatogenesis

Abstract: Two miRNA clusters, miR-34b/c and miR-449, are essential for normal brain development, motile ciliogenesis, and spermatogenesis

Cited by 251 publications

References 31 publications

MicroRNAs and DNA methylation as epigenetic regulators of mitosis, meiosis and spermiogenesis

MicroRNAs and DNA methylation as epigenetic regulators of mitosis, meiosis and spermiogenesis

MicroRNA profling in ethylene glycol monomethyl ether-induced monkey testicular toxicity model

Characterizing isomiR variants within the microRNA‐34/449 family

Contact Info

Product

Resources

About