PLoS One
·
2016
·Vol. 11
·期 10
·e0163340
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IF 3.057
Hong Zhou,Yapei Wang,Qiongying Lv,Juan Zhang,Qing Wang,Fei Gao,Haoli Hou,Hao Zhang,Wei Zhang,Lijia Li
The ribosomal RNA (rRNA) gene encodes rRNA for protein synthesis. Aberrant expression of the rRNA gene has been generally observed in tumor cells and levels of its promoter methylation as an epigenetic regulator affect rRNA gene transcription. The possible relationship between expression and promoter methylation of rDNA has not been examined in human clinical cervical cancer. Here we investigate rRNA gene expression by quantitative real time PCR, and promoter methylation levels by HpaII/MspI digestion and sodium bisulfite sequencing in the development of human cervical cancer. We find that indeed rRNA levels are elevated in most of cervical intraepithelial neoplasia (CIN) specimens as compared with non-cancer tissues. The rDNA promoter region in cervical intraepithelial neoplasia (CIN) tissues reveals significant hypomethylation at cytosines in the context of CpG dinucleotides, accompanied with rDNA chromatin decondensation. Furthermore treatment of HeLa cells with the methylation inhibitor drug 5-aza-2’-deoxycytidine (DAC) demonstrates the negative correlation between the expression of 45S rDNA and the methylation level in the rDNA promoter region. These data suggest that a decrease in rDNA promoter methylation levels can result in an increase of rRNA synthesis in the development of human cervical cancer.
研究领域:
分子生物学
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肿瘤学
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表观遗传学
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DOI
PubMed
高影响因子
JOURNAL OF HAZARDOUS MATERIALS
·
2023
·
IF 13.6
Renzhang Lin,Hao Wu,Xiangyu Kong,Hao Ren,Zhenmei Lu
The lack of universal indicators for predicting microbial biodegradation potential and assessing remediation effects limits the generalization of bioremediation. The community-level ribosomal RNA gene operon (rrn) copy number, an important functional trait, has the potential to serve as a key indicator of the bioremediation of organic pollutants . A meta-analysis based on 1275 samples from 26 hydrocarbon-related studies revealed a positive relationship between the microbial hydrocarbon biodegradation level and the community-level rrn copy number in soil, seawater and culture. Subsequently, a microcosm experiment was performed to decipher the community-level rrn copy number response mechanism during total petroleum hydrocarbon (TPH) biodegradation. The treatment combining straw with resuscitation-promoting factor (Rpf) exhibited the highest community-level rrn copy number and the most effective biodegradation compared with other treatments, and the initial TPH content (20,000 mg kg -1 ) was reduced by 67.67% after 77 days of incubation. TPH biodegradation rate was positively correlated with the average community-level rrn copy number ( p = 0.001, R 2 = 0.5781). Both meta and community analyses showed that rrn copy number may reflect the potential of hydrocarbon degradation and microbial dormancy. Our findings provide insight into the applicability of the community-level rrn copy number to assess bacterial biodegradation for pollution remediation.
研究领域:
环境科学
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微生物学
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产品关联
DOI
PubMed
高影响因子
MOLECULAR THERAPY
·
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
MOLECULAR CELL
·
2024
·
IF 14.5
Yu-Meng Sun,Shun-Xin Zhu,Xiao-Tong Chen,Qi Pan,Yan An,Tian-Qi Chen,Heng-Jing Huang,Ke-Jia Pu,Jun-Yi Lian,Wen-Long Zhao,Wen-Tao Wang,Yue-Qin Chen
Liquid-to-solid phase transition of proteins with prion-like domains (PLDs) has been associated with neurodegenerative diseases and aging. High protein concentration is one important aspect triggering the transition; however, several prion-like proteins, including fibrillarin (FBL), an important phase-separated protein in the nucleolus for pre-rRNA processing, show relatively high expression levels in certain cells, especially cancer cells, without obvious phase transitions and growth arrest. How cells maintain prion-like protein proteostasis is still unknown. Here, we attempt to answer the question, with FBL as an example. We find that lncRNA DNAJC3-AS1 can buffer the behavior of FBL condensation and maintain the state and function of fibrillar component/dense fibrillar component (FC/DFC) units in human cell lines through two mechanisms, not only facilitating FBL condensation but also inhibiting excessive aggregation by binding multiple PLDs and partially blocking their interactions. We propose that lncRNAs could supply buffered systems to sustain functional phase states of prion-like proteins.
研究领域:
分子生物学
·
细胞生物学
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遗传学
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癌症研究
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产品关联
DOI
PubMed
高影响因子
Cell Reports
·
2024
·
IF 7.5
Sijia Ren,Feng Bai,Viviane Schnell,Clara Stanko,Muriel Ritsch,Tino Schenk,Emanuel Barth,Manja Marz,Bin Wang,Xin-Hai Pei,Holger Bierhoff
Extensive remodeling of the female mammary epithelium during development and pregnancy has been linked to cancer susceptibility. The faithful response of mammary epithelial cells (MECs) to hormone signaling is key to avoiding breast cancer development. Here, we show that lactogenic differentiation of murine MECs requires silencing of genes encoding ribosomal RNA (rRNA) by the antisense transcript PAPAS. Accordingly, knockdown of PAPAS derepresses rRNA genes, attenuates the response to lactogenic hormones, and induces malignant transformation. Restoring PAPAS levels in breast cancer cells reduces tumorigenicity and lung invasion and activates many interferon-regulated genes previously linked to metastasis suppression. Mechanistically, PAPAS transcription depends on R-loop formation at the 3' end of rRNA genes, which is repressed by RNase H1 and replication protein A (RPA) overexpression in breast cancer cells. Depletion of PAPAS and upregulation of RNase H1 and RPA in human breast cancer underpin the clinical relevance of our findings.
研究领域:
癌症生物学
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分子生物学
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细胞生物学
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DOI
PubMed
高影响因子
Advanced Therapeutics
·
2024
·Vol. 7
·期 11
·2400275
·
IF 3.7
Yao Yao,Binqing Xue,Duncan James Lessing,Weihua Chu
Alterations in the intestinal microenvironment, including increased levels of reactive oxygen species (ROS), abnormalities in intestinal mucosal immune regulation, and dysbiosis of the intestinal microbiota, are crucial to the development of inflammatory bowel disease (IBD). Herein, an oral colon-targeting Se-Probiotic@Alginate bead (BLSe) with ROS-scavenging ability and gut immune-microbiota microenvironment remodeling ability is developed using alginate as the primary outer shell encapsulated with probiotics Bacillus licheniformis (BL) and selenium nanoparticles stabilized by yeast glucan (SeNPs). In vitro studies have shown that SeNPs possess antioxidant activity and BLSe exhibits excellent stability in gastric fluids and are released in intestinal fluids. In vivo studies have also shown that BLSe significantly alleviated dextran sulphate sodium (DSS)-induced colitis in mice by inhibiting colon shortening, enhancing antioxidant activity, reducing pro-inflammatory cytokine secretion, and protecting the intestinal mucosal barrier. 16S ribosomal RNA sequencing shows that BLSe can remodel the composition of the gut microbiota by improving bacterial diversity and restoring the relative abundance of beneficial bacteria in the colon. Overall, this study advances a promising probiotic-based nanomedicine for managing IBD.
研究领域:
药学
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免疫学
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微生物学
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胃肠病学
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产品关联
DOI
高影响因子
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