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Knockout of glutathione peroxidase 5 down-regulates the pirnas in the caput epididymidis of aged mice

Asian Journal of Andrology 2020年第6期22卷 590-601页

作者： Chen Chu Lu Yu Joelle Henry-Berger Yan-Fei Ru Ayhan Kocer Alexandre Champroux Zhi-Tong Li Miao He Sheng-Song Xie Wu-Bin Ma Min-Jie Ni Zi-Mei Ni Yun-Li Guo Zhao-Liang Fei Lan-Tao Gou Qiang Liu Samanta Sharma Yu Zhou Mo-Fang Liu Charlie Degui Chen Andrew L Eamens Brett Nixon Yu-Chuan Zhou Joel R Drevet Yong-Lian Zhang State Key Laboratory of Molecular Biology Shanghai Key Laboratory of Molecular AndrologyCAS Center for Excellence in Molecular Cell ScienceShanghai Institute of Biochemistry and Cell BiologyChinese Academy of SciencesUniversity of Chinese Academy of SciencesShanghai 200031China Genetics Reproduction and Development Laboratory CNRS UMR 6293-INSERM U1103-Universite Clermont AuvergneClermont-Ferrand 63001France Institute of Neuroscience State Key Laboratory of NeuroscieneeShanghai Institutes for Biological SciencesChinese Academy of SciencesShanghai 200031China Key Laboratory of Agricultural Animal Genetics Breedingand Reproduction of the Ministry of Education and Key Laboratory of Swine Genetics and Breeding of the Ministry of AgricultureHuazhong Agricultural UniversityWuhan 430070China Department of Cellular and Molecular Medicine University of CaliforniaSan DiegoLa JollaCA 92093-0651USA Department of Anatomy Histology and EmbryologyShanghai Jiao long University School of MedicineShanghai Key Laboratory of Reproductive MedicineShanghai 200025China department of Cancer Biology Dana-Farber Cancer InstituteBostonMA 02215USA Department of Genetics Harvard Medical SchoolBostonMA 02115USA Priority Research Centre for Reproductive Sciences School of Environmental and Life SciencesThe University of NewcastleCallaghanNSW 2308Australia.

The mammalian epididymis not only plays a fun dame ntal role in the maturati on of spermatozoa,but also provides protecti on agai nst various *** foremost among these is the threat posed by oxidative stress,which arises from an imbalance in reactive oxygen species and can elicit damage to cellular lipids,proteins,and nucleic *** mice,the risk of oxidative damage to spermatozoa is mitigated through the expression and secretion of glutathione peroxidase 5(GPX5)as a major luminal scavenger in the proximal caput epididymidal ***,the loss of GPX5^-/-mediated protection leads to impaired DNA integrity in the spermatozoa of aged Gpx57 *** explore the underlying mechanism,we have conducted transcriptomic analysis of caput epididymidal epithelial cells from aged(13 months old)Gpx5^-/-m *** analysis revealed the dysregulation of several thousand epididymal mrna transcripts,in eluding the downregulation of a subgroup of pirna pathway gen es,in aged Gpx5^-/-*** agreeme nt with these fin dings,we also observed the loss of pirnas,which potentially bind to the P-element-induced wimpy testis(PlWI)-like proteins PIWIL1 and *** absence of these pirnas was correlated with the elevated mrna levels of their putative gene targets in the caput epididymidis of Gpx5^-/-***,the oxidative stress response genes tend to have more targeting pirnas,and many of them were among the top increased genes upon the loss of GPX5^-/-.Taken together,our findings suggest the existence of a previously uncharacterized somatic pirna pathway in the mammalian epididymis and its possible invoIvement in the aging and oxidative stress-mediated responses.

关键词： epididymis GPX5 oxidative stress pirna PIWI-interacting rna small noncoding rna

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Design of artificial small regulatory trans-rna for gene knockdown in Bacillus subtilis

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Synthetic and Systems Biotechnology 2023年第1期8卷 61-68页

作者： Guobin Yin Anqi Peng Luyao Zhang Yang Wang Guocheng Du Jian Chen Zhen Kang The Science Center for Future Foods Jiangnan UniversityWuxi214122China The Key Laboratory of Carbohydrate Chemistry and Biotechnology Ministry of EducationSchool of BiotechnologyJiangnan UniversityWuxi214122China The Key Laboratory of Industrial Biotechnology Ministry of EducationSchool of BiotechnologyJiangnan UniversityWuxi214122China

Bacillus subtilis as the Gram-positive model bacterium has been widely used in synthetic biology and biotechnology while the regulatory rna tools for *** are still not fully ***,a bottom-up approach is proposed for designing artificial trans-acting *** engineering the intrinsic srna SR6,a minimized core scaffold structure consisting of an 8 bp stem,a 4 nt loop,and a 9 nt polyU tail was generated and proven to be sufficient for constructing srnas with strong repression activity(83%).Moreover,we demonstrate this artificial srna system functions well in an hfq-independent manner and also achieves strong repression efficiency in Escherichia coli(above 80%).A structure-based srna design principle was further developed for the automatic generation of custom srnas with this core scaffold but various sequences,which facilitates the manipulation and avoids structure disruption when fusing any base-pairing *** applying these auto-designed srnas,we rapidly modified the cell morphology and biofilm formation,and regulated metabolic flux toward acetoin *** srna system with cross-species regulatory activities not only enriched the gene regulation toolkit in synthetic biology for *** and *** but also enhanced our understanding of trans-acting srnas.

关键词： Gene knockdown Posttranscriptional regulation small noncoding rna Synthetic biology Cross-species Bacillus subtilis

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