MOLECULAR THERAPY
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2025
·
IF 12
Mengya Zhang,Xueguang Zhang,Chen Tan,Ting Jiang,Zheng Cao,Yufei Chen,Feng Qiao,Gelin Huang,Chaoye Ma,Huixia Li,Mei Ye,Lei Wang,Liandong Zuo,Jun Yu,Xiaofeng Li,Yunfang Zhang,Yue-Qiu Tan,Shuibin Lin,Wenming Xu,Hao Chen
Recent studies have highlighted RNA modifications as integral regulators of gene expression during spermatogenesis. Ribosomal RNAs (rRNAs) are the most abundant RNA in cells, while the function and clinical relevance of rRNA modifications in spermatogenesis remain poorly understood. Here, we identified 4 pathogenic heterozygous variants of METTL5 in 1,427 patients with male infertility characterized as oligoasthenoteratozoospermia (OAT). The pathogenic variants of METTL5 led to the significantly decreased expression level of METTL5. Null mutation of 18S rRNA methyltransferase Mettl5 led to male infertility attributed to OAT during spermiogenesis, presenting defects in both the sperm head and tail. Notwithstanding the absence of notable changes in global translation after Mettl5 loss, we observed a compromised translational efficiency of mRNAs encoding proteins crucial for spermiogenesis, including Gk2 , Akap4 , Fsip2 , Odf2 , and Pgk2 . Intriguingly, therapeutic interventions via intracytoplasmic sperm injection in OAT couples with these variants resulted in successful pregnancies. These insights not only identify METTL5-mediated 18S rRNA m 6 A modification as a novel genetic determinant for OAT but also offer a new target to the genetic counseling, clinical diagnosis, and potential treatment strategies for male infertility.
研究领域:
分子生物学
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遗传学
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生殖医学
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RNA修饰
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发育生物学
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产品关联
DOI
PubMed
高影响因子
REPRODUCTION
·
2022
·
IF 3.923
Luchun Zhang,Meng Yuan,Xingwei Huang,Qianzi Cao,Shaogang Huang,Ruizhen Sun,Lei Lei
In brief: Several factors affect the reprogramming efficiency of nuclear transfer embryos. This study shows that inhibiting 18S rRNA m6A methyltransferase METTL5 during nuclear transfer can improve the developmental rate of nuclear transfer embryos. Abstract: N6-methyladenosine (m6A) is one of the most important epigenetic modifications in eukaryotic RNAs, which regulates development and diseases. It is identified by several proteins. Methyltransferase-like 5 (METTL5), an enzyme that methylates 18S rRNA m6A, controls the translation of proteins and regulates pluripotency in embryonic stem cells. However, the functions of METTL5 in embryonic development have not been explored. Here, we found that Mettl5 was upregulated in somatic cell nuclear transfer (SCNT) embryos compared with normal fertilized embryos. Therefore, we hypothesized that METTL5 knockdown during the early stage of SCNT would improve the developmental rate of SCNT embryos. Notably, injection of Mettl5 siRNA (si-Mettl5) into enucleated oocytes during nuclear transfer increased the rate of development and the number of cells in blastocysts. Moreover, inhibition of METTL5 reduced the activity of phosphorylated ribosomal protein S6, decreased the levels of the repressive histone modification H3K27me3 and increased the expression of activating histone modifications H3K27ac and H3K4me3 and mRNA levels of some 2-cell-specific genes. These results expand our understanding of the role of METTL5 in early embryonic development and provide a novel idea for improving the efficiency of nuclear transfer cloning.
研究领域:
分子生物学
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生殖生物学
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表观遗传学
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产品关联
DOI
PubMed
高影响因子
Frontiers in Microbiology
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2015
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IF 3.989
Chen Lin,Xu Jianming,Feng Youzhi,Wang Juntao,Yu Yongjie,Brookes Philip C.
In soil microbiology, there is a “paradox” of soil organic carbon (SOC) mineralization, which is that even though chloroform fumigation destroys majority of the soil microbial biomass, SOC mineralization continues at the same rate as in the non-fumigated soil during the incubation period. Soil microeukaryotes as important SOC decomposers, however, their community-level responses to chloroform fumigation are not well understood. Using the 18S rRNA gene amplicon sequencing, we analyzed the composition, diversity, and C-metabolic functions of a grassland soil and an arable soil microeukaryotic community in response to fumigation followed by a 30-day incubation. The grassland and arable soil microeukaryotic communities were dominated by the fungal Ascomycota (80.5–93.1% of the fungal sequences), followed by the protistan Cercozoa and Apicomplexa. In the arable soil fungal community, the predominance of the class Sordariomycetes was replaced by the class Eurotiomycetes after fumigation at days 7 and 30 of the incubation. Fumigation changed the microeukaryotic α-diversity in the grassland soil at days 0 and 7, and β-diversity in the arable soil at days 7 and 30. Network analysis indicated that after fumigation fungi were important groups closely related to other taxa. Most phylotypes (especially Sordariomycetes, Dothideomycetes, Coccidia, and uncultured Chytridiomycota) were inhibited, and only a few were positively stimulated by fumigation. Despite the inhibited Sordariomycetes, the fumigated communities mainly consisted of Eurotiomycetes and Sordariomycetes (21.9 and 36.5% relative frequency, respectively), which are able to produce hydrolytic enzymes associated with SOC mineralization. Our study suggests that fumigation not only decreases biomass size, but modulates the composition and diversity of the soil microeukaryotic communities, which are capable of driving SOC mineralization by release of hydrolytic enzymes during short-term fumigation-incubation.
研究领域:
土壤微生物学
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环境科学
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分子生态学
✓ 已验证
DOI
PubMed
高影响因子
Chemical Science
·
2021
·Vol. 12
·期 23
·8149-8156
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IF 9.825
Ming-Yu Cheng,Xue-Jiao You,Jiang-Hui Ding,Yi Dai,Meng-Yuan Chen,Bi-Feng Yuan,Yu-Qi Feng
RNA modifications play critical roles in regulating a variety of physiological processes. Methylation is the most prevalent modification occurring in RNA. Three isomeric cytidine methylation modifications have been reported in RNA, including 3-methylcytidine (m3C), N4-methylcytidine (m4C), and 5-methylcytidine (m5C), in mammals. Aside from the single methylation on the nucleobase of cytidines, dual methylation modifications occurring in both the 2′ hydroxyl of ribose and the nucleobase of cytidines also have been reported, including N4,2′-O-dimethylcytidine (m4Cm) and 5,2′-O-dimethylcytidine (m5Cm). m4Cm has been found in the 16S rRNA of E. coli, while m5Cm has been found in the tRNA of terminal thermophilic archaea and mammals. However, unlike m4Cm and m5Cm, the presumed dual methylation of 3,2′-O-dimethylcytidine (m3Cm) has never been discovered in living organisms. Thus, the presence of m3Cm in RNA remains an open question. In the current study, we synthesized m3Cm and established a liquid chromatography-electrospray ionization-tandem mass spectrometry (LC-ESI-MS/MS) method to determine the dimethylation of cytidines, m3Cm, m4Cm and m5Cm. Under optimized analytical conditions, m3Cm, m4Cm and m5Cm can be clearly distinguished. Using the method, we discovered the existence of m3Cm in the RNA of mammals. The identified m3Cm is a novel modification that hasn't been reported in the three-domain system, including archaea, bacteria, and eukaryotes. We confirmed that m3Cm mainly existed in the small RNA (<200 nt) of mammals. In addition, we identified, for the first time, the presence of m4Cm in the 18S rRNA of mammalian cells. The stable isotope tracing monitored by mass spectrometry demonstrated that S-adenosyl-L-methionine was a methyl donor for all three dimethylations of cytidines in RNA. The discovery of m3Cm broadens the diversity of RNA modifications in living organisms. In addition, the discovery of m3Cm and m4Cm in mammals opens new directions in understanding RNA modification-mediated RNA processing and gene expression regulation.
研究领域:
分子生物学
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生物化学
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RNA生物学
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DOI
PubMed
高影响因子
ENVIRONMENTAL POLLUTION
·
2020
·
IF 6.793
Tao Lu,Nuohan Xu,Qi Zhang,Zhenyan Zhang,Andries Debognies,Zhigao Zhou,Liwei Sun,Haifeng Qian
Glyphosate , one of the most popular herbicides, has become a prominent aquatic contaminant because of its huge usage. The eco-safety of glyphosate is still in controversy, and it is inconclusive how glyphosate influences aquatic microbial communities . In the present study, the effects of glyphosate on the structure and function of microbial communities in a freshwater microcosm were investigated. 16S/18S rRNA gene sequencing results showed that glyphosate treatment (2.5 mg L −1 , 15 days) did not significantly alter the physical and chemical condition of the microcosm or the composition of the main species in the community, but metatranscriptomic analyses indicated that the transcriptions of some cyanobacteria were significantly influenced by glyphosate. The microbial community enhanced the gene expression in pathways related to translation, secondary metabolites biosynthesis, transport and catabolism to potentially withstand glyphosate contamination. In the low phosphorus (P) environment, a common cyanobacterium, Synechococcus , plays a special role by utilizing glyphosate as P source and thus reducing its toxicity to other microbes, such as Pseudanabaena . In general, addition of glyphosate in our artificial microcosms did not strongly affect the aquatic microbial community composition but did alter the community’s transcription levels, which might be potentially explained by that some microbes could alleviate glyphosate’s toxicity by utilizing glyphosate as a P source.
研究领域:
环境科学
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微生物学
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生态学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）