The small-angle neutron scattering(SANS)instrument,one of the first three instruments of the China Spallation Neutron Source(CSNS),is designed to probe the microscopic and mesoscopic structures of materials in the sca...The small-angle neutron scattering(SANS)instrument,one of the first three instruments of the China Spallation Neutron Source(CSNS),is designed to probe the microscopic and mesoscopic structures of materials in the scale range 1–100 nm.A large-area ^(3)He tube array detector has been constructed and operates at the CSNS SANS instrument since August 2018.It consists of 120 linear position-sensitive detector tubes,each 1 m in length and 8 mm in diameter,and filled with ^(3)He gas at 20 bar to obtain a high detection efficiency.The ^(3)He tubes were divided into ten modules,providing an overall area of 1000 mm×1020 mm with a high count rate capability.Because each tube is installed independently,the detector can be quickly repaired in situ by replacing damaged tubes.To reduce air scattering,the SANS detector must operate in a vacuum environment(0.1 mbar).An all-metal sealing technique was adopted to avoid high-voltage breakdown by ensuring a high-voltage connection and an electronic system working in an atmospheric environment.A position resolution of 7.8±0.1 mm(full width at maximum)is measured along the length of the tubes,with a high detection efficiency of 81±2% at 2A.Operating over the past four years,the detector appears to perform well and with a high stability,which supports the SANS instrument to finish approximately 200 user scientific programs.展开更多
PIWI-clade proteins harness pi RNAs of 24–33 nt in length.Of great puzzles are how PIWI-clade proteins incorporate pi RNAs of different sizes and whether the size matters to PIWI/pi RNA function.Here we report that a...PIWI-clade proteins harness pi RNAs of 24–33 nt in length.Of great puzzles are how PIWI-clade proteins incorporate pi RNAs of different sizes and whether the size matters to PIWI/pi RNA function.Here we report that a PIWI-Ins module unique in PIWIclade proteins helps define the length of pi RNAs.Deletion of PIWI-Ins in Miwi shifts MIWI to load with shorter pi RNAs and causes spermiogenic failure in mice,demonstrating the functional importance of this regulatory module.Mechanistically,we show that longer pi RNAs provide additional complementarity to target m RNAs,thereby enhancing the assembly of the MIWI/e IF3f/Hu R super-complex for translational activation.Importantly,we identify a c.1108C>T(p.R370W)mutation of HIWI(human PIWIL1)in infertile men and demonstrate in Miwi knock-in mice that this genetic mutation impairs male fertility by altering the property of PIWI-Ins in selecting longer pi RNAs.These findings reveal a critical role of PIWI-Ins-ensured longer pi RNAs in fine-tuning MIWI/pi RNA targeting capacity,proven essential for spermatid development and male fertility.展开更多
Chemical modifications expand the composition of RNA molecules from four standard nucleosides to over 160 modified nucleosides,which greatly increase the complexity and utility of RNAs.Transfer RNAs(tRNAs)are the most...Chemical modifications expand the composition of RNA molecules from four standard nucleosides to over 160 modified nucleosides,which greatly increase the complexity and utility of RNAs.Transfer RNAs(tRNAs)are the most heavily modified cellular RNA molecules and contain the largest variety of modifications.Modification of tRNAs is pivotal for protein synthesis and also precisely regulates the noncanonical functions of tRNAs.Defects in tRNA modifications lead to numerous human diseases.Up to now,more than 100 types of modifications have been found in tRNAs.Intriguingly,some modifications occur widely on all tRNAs,while others only occur on a subgroup of tRNAs or even only a specific tRNA.The modification frequency of each tRNA is approximately 7% to 25%,with 5-20 modification sites present on each tRNA.The occurrence and modulation of tRNA modifications are specifically noticeable as plenty of interplays among different sites and modifications have been discovered.In particular,tRNA modifications are responsive to environmental changes,indicating their dynamic and highly organized nature.In this review,we summarized the known occurrence order,cross-talk,and cooperativity of tRNA modifications.展开更多
基金supported by the National Key R&D Program of China(No.2021YFA1600703)the National Natural Science Foundation of China(No.12175254)+2 种基金the Youth Innovation Promotion Association CASthe China Spallation Neutron Source Projectthe Innovative Projects of the IHEP(No.E15459U210).
文摘The small-angle neutron scattering(SANS)instrument,one of the first three instruments of the China Spallation Neutron Source(CSNS),is designed to probe the microscopic and mesoscopic structures of materials in the scale range 1–100 nm.A large-area ^(3)He tube array detector has been constructed and operates at the CSNS SANS instrument since August 2018.It consists of 120 linear position-sensitive detector tubes,each 1 m in length and 8 mm in diameter,and filled with ^(3)He gas at 20 bar to obtain a high detection efficiency.The ^(3)He tubes were divided into ten modules,providing an overall area of 1000 mm×1020 mm with a high count rate capability.Because each tube is installed independently,the detector can be quickly repaired in situ by replacing damaged tubes.To reduce air scattering,the SANS detector must operate in a vacuum environment(0.1 mbar).An all-metal sealing technique was adopted to avoid high-voltage breakdown by ensuring a high-voltage connection and an electronic system working in an atmospheric environment.A position resolution of 7.8±0.1 mm(full width at maximum)is measured along the length of the tubes,with a high detection efficiency of 81±2% at 2A.Operating over the past four years,the detector appears to perform well and with a high stability,which supports the SANS instrument to finish approximately 200 user scientific programs.
基金supported by the National Key Research and Development Program of China(2022YFA1303300,2021YFC2700200,2017YFA0504400)Chinese Academy of Sciences(“Strategic Priority Research Program”grants XDB37000000)+3 种基金the National Natural Science Foundation of China(31830109,31821004,91940305,31961133022,32101037,32271347,21933010,22203089)Science and Technology Commission of Shanghai Municipality(17JC1420100,2017SHZDZX01,19JC1410200,21YF1452700,21ZR1470500)the Young Elite Scientist Sponsorship Program of the China Association for Science and Technology(2021QNRC001)the Foundation of Key Laboratory of Gene Engineering of the Ministry of Education。
文摘PIWI-clade proteins harness pi RNAs of 24–33 nt in length.Of great puzzles are how PIWI-clade proteins incorporate pi RNAs of different sizes and whether the size matters to PIWI/pi RNA function.Here we report that a PIWI-Ins module unique in PIWIclade proteins helps define the length of pi RNAs.Deletion of PIWI-Ins in Miwi shifts MIWI to load with shorter pi RNAs and causes spermiogenic failure in mice,demonstrating the functional importance of this regulatory module.Mechanistically,we show that longer pi RNAs provide additional complementarity to target m RNAs,thereby enhancing the assembly of the MIWI/e IF3f/Hu R super-complex for translational activation.Importantly,we identify a c.1108C>T(p.R370W)mutation of HIWI(human PIWIL1)in infertile men and demonstrate in Miwi knock-in mice that this genetic mutation impairs male fertility by altering the property of PIWI-Ins in selecting longer pi RNAs.These findings reveal a critical role of PIWI-Ins-ensured longer pi RNAs in fine-tuning MIWI/pi RNA targeting capacity,proven essential for spermatid development and male fertility.
基金supported by the National Key Research and Development Program of China(2020YFA0803400)the National Natural Science Foundation of China(32022040,31971230,31770842)the China Postdoctoral Science Foundation Grants(2020M671253)。
文摘Chemical modifications expand the composition of RNA molecules from four standard nucleosides to over 160 modified nucleosides,which greatly increase the complexity and utility of RNAs.Transfer RNAs(tRNAs)are the most heavily modified cellular RNA molecules and contain the largest variety of modifications.Modification of tRNAs is pivotal for protein synthesis and also precisely regulates the noncanonical functions of tRNAs.Defects in tRNA modifications lead to numerous human diseases.Up to now,more than 100 types of modifications have been found in tRNAs.Intriguingly,some modifications occur widely on all tRNAs,while others only occur on a subgroup of tRNAs or even only a specific tRNA.The modification frequency of each tRNA is approximately 7% to 25%,with 5-20 modification sites present on each tRNA.The occurrence and modulation of tRNA modifications are specifically noticeable as plenty of interplays among different sites and modifications have been discovered.In particular,tRNA modifications are responsive to environmental changes,indicating their dynamic and highly organized nature.In this review,we summarized the known occurrence order,cross-talk,and cooperativity of tRNA modifications.