Pancreatic ribonuclease(RNase1),a digestive enzyme produced by the pancreas,is associated with the functional adaptation of dietary habits and is regarded as an attractive model system for studies of molecular evoluti...Pancreatic ribonuclease(RNase1),a digestive enzyme produced by the pancreas,is associated with the functional adaptation of dietary habits and is regarded as an attractive model system for studies of molecular evolution.In this study,we identified 218 functional genes and 48 pseudogenes from 114 species that span all four Cetartiodactyla lineages:two herbivorous lineages(Ruminantia and Tylopoda)and two non-herbivorous lineages(Cetancodonta and Suoidea).Multiple RNase1 genes were detected in all species of the two herbivorous lineages,and phylogenetic and genomic location analyses demonstrated that independent gene duplication events occurred in Ruminantia and Tylopoda.In Ruminantia,the gene duplication events occurred in the ancestral branches of the lineage in theMiddle Eocene,a time of increasing climatic seasonality during which Ruminantia rapidly radiated.In contrast,only a single RNase1 gene was observed in the species of the two non-herbivorous lineages(Cetancodonta and Suoidea),suggesting that the previous Cetacea-specific loss hypothesis should be rejected.Moreover,the duplicated genes of RNase1 in the two herbivorous lineages(Ruminantia and Tylopoda)may have undergone functional divergence.In combination with the temporal coincidence between gene replication and the enhanced climatic seasonality during theMiddle Eocene,this functional divergence suggests that RNase1 gene duplication was beneficial for Ruminantia to use the limited quantities of sparse fibrous vegetation and adapt to seasonal changes in climate.In summary,the findings indicate a complex and intriguing evolutionary pattern of RNase1 in Cetartiodactyla and demonstrate the molecular mechanisms by which organisms adapt to the environment.展开更多
An S-like RNase cDNA had been isolated from common wheat (Triticum aestivum L). The transcription of WRN1 mRNA was down-regulated by natural- and dark-induced senescence. But it was not senile-tissue-specific. As the ...An S-like RNase cDNA had been isolated from common wheat (Triticum aestivum L). The transcription of WRN1 mRNA was down-regulated by natural- and dark-induced senescence. But it was not senile-tissue-specific. As the two key histidine residues were replaced, WRN1 may not be active as RNase. Southern blotting analysis showed that WRN1 exists as one of a small gene family in common wheat genome.展开更多
R-loops play various roles in many physiological processes,however,their role in meiotic division remains largely unknown.Here we show that R-loops and their regulator RNase H1 are present at centromeres during oocyte...R-loops play various roles in many physiological processes,however,their role in meiotic division remains largely unknown.Here we show that R-loops and their regulator RNase H1 are present at centromeres during oocyte meiotic divisions.Proper centromeric R-loops are essential to ensure chromosome alignment in oocytes during metaphase I(MI).Remarkably,both Rnaseh1 knockout and overexpression in oocytes lead to severe spindle assembly defects and chromosome misalignment due to dysregulation of R-loops at centromeres.Furthermore,we find that replication protein A(RPA)is recruited to centromeric R-loops,facilitating the deposition of ataxia telangiectasia-mutated and Rad3-related(ATR)kinase at centromeres by interacting with the ATR-interaction protein(ATRIP).The ATR kinase deposition triggers the activity of CHK1,stimulating the phosphorylation of Aurora B to finally promote proper spindle assembly and chromosome alignment at the equatorial plate.Most importantly,the application of ATR,CHK1,and Aurora B inhibitors could efficiently rescue the defects in spindle assembly and chromosome alignment due to RNase H1 deficiency in oocytes.Overall,our findings uncover a critical role of R-loops during mouse oocyte meiotic divisions,suggesting that dysregulation of R-loops may be associated with female infertility.Additionally,ATR,CHK1,and Aurora B inhibitors may potentially be used to treat some infertile patients.展开更多
Circular intronic RNAs(ci RNAs) escaping from DBR1 debranching of intron lariats are co-transcriptionally produced from prem RNA splicing, but their turnover and mechanism of action have remained elusive. We report th...Circular intronic RNAs(ci RNAs) escaping from DBR1 debranching of intron lariats are co-transcriptionally produced from prem RNA splicing, but their turnover and mechanism of action have remained elusive. We report that RNase H1 degrades a subgroup of ci RNAs in human cells. Many ci RNAs contain high GC% and tend to form DNA:RNA hybrids(R-loops) for RNase H1 cleavage, a process that appears to promote Pol II transcriptional elongation at ci RNA-producing loci. One ci RNA, ciankrd52, shows a stronger ability of R-loop formation than that of its cognate pre-m RNA by maintaining a locally open RNA structure in vitro. This allows the release of pre-m RNA from R-loops by ci-ankrd52 replacement and subsequent ci RNA removal via RNase H1 for efficient transcriptional elongation. We propose that such an R-loop dependent ci RNA degradation likely represents a mechanism that on one hand limits ci RNA accumulation by recruiting RNase H1 and on the other hand resolves Rloops for transcriptional elongation at some GC-rich ci RNA-producing loci.展开更多
基金supported by the Special Basic Cooperative Research Programs of Yunnan Province Youth Academic and Technical Leaders Reserve Talent(202405AC350082)Yunnan Provincial Undergraduate Universities’Association(202101BA070001-068).
文摘Pancreatic ribonuclease(RNase1),a digestive enzyme produced by the pancreas,is associated with the functional adaptation of dietary habits and is regarded as an attractive model system for studies of molecular evolution.In this study,we identified 218 functional genes and 48 pseudogenes from 114 species that span all four Cetartiodactyla lineages:two herbivorous lineages(Ruminantia and Tylopoda)and two non-herbivorous lineages(Cetancodonta and Suoidea).Multiple RNase1 genes were detected in all species of the two herbivorous lineages,and phylogenetic and genomic location analyses demonstrated that independent gene duplication events occurred in Ruminantia and Tylopoda.In Ruminantia,the gene duplication events occurred in the ancestral branches of the lineage in theMiddle Eocene,a time of increasing climatic seasonality during which Ruminantia rapidly radiated.In contrast,only a single RNase1 gene was observed in the species of the two non-herbivorous lineages(Cetancodonta and Suoidea),suggesting that the previous Cetacea-specific loss hypothesis should be rejected.Moreover,the duplicated genes of RNase1 in the two herbivorous lineages(Ruminantia and Tylopoda)may have undergone functional divergence.In combination with the temporal coincidence between gene replication and the enhanced climatic seasonality during theMiddle Eocene,this functional divergence suggests that RNase1 gene duplication was beneficial for Ruminantia to use the limited quantities of sparse fibrous vegetation and adapt to seasonal changes in climate.In summary,the findings indicate a complex and intriguing evolutionary pattern of RNase1 in Cetartiodactyla and demonstrate the molecular mechanisms by which organisms adapt to the environment.
文摘An S-like RNase cDNA had been isolated from common wheat (Triticum aestivum L). The transcription of WRN1 mRNA was down-regulated by natural- and dark-induced senescence. But it was not senile-tissue-specific. As the two key histidine residues were replaced, WRN1 may not be active as RNase. Southern blotting analysis showed that WRN1 exists as one of a small gene family in common wheat genome.
基金supported by the National Natural Science Foundation of China(32230029,81925015,32270898,32400709,and 32400714)the National Key Research and Development Program of China(2022YFC2702600)+2 种基金the China Postdoctoral Science Foundation(2024M760638 and 2024M760640)the Science and Technology Project of Guangzhou(2023A03J0886)the plan on enhancing scientific research in GMU.
文摘R-loops play various roles in many physiological processes,however,their role in meiotic division remains largely unknown.Here we show that R-loops and their regulator RNase H1 are present at centromeres during oocyte meiotic divisions.Proper centromeric R-loops are essential to ensure chromosome alignment in oocytes during metaphase I(MI).Remarkably,both Rnaseh1 knockout and overexpression in oocytes lead to severe spindle assembly defects and chromosome misalignment due to dysregulation of R-loops at centromeres.Furthermore,we find that replication protein A(RPA)is recruited to centromeric R-loops,facilitating the deposition of ataxia telangiectasia-mutated and Rad3-related(ATR)kinase at centromeres by interacting with the ATR-interaction protein(ATRIP).The ATR kinase deposition triggers the activity of CHK1,stimulating the phosphorylation of Aurora B to finally promote proper spindle assembly and chromosome alignment at the equatorial plate.Most importantly,the application of ATR,CHK1,and Aurora B inhibitors could efficiently rescue the defects in spindle assembly and chromosome alignment due to RNase H1 deficiency in oocytes.Overall,our findings uncover a critical role of R-loops during mouse oocyte meiotic divisions,suggesting that dysregulation of R-loops may be associated with female infertility.Additionally,ATR,CHK1,and Aurora B inhibitors may potentially be used to treat some infertile patients.
基金This work was supported by the National Natural Science Foundation of China(NSFC)(91940303,31725009)the HHMI International Program(55008728)to L.-L.C.+2 种基金NSFC(31730111,31925011)to L.Y.Young Elite Scientists Sponsorship Program(2020QNRC001)to X.L.L.-L.C.the support from the XPLORER PRIZE.
文摘Circular intronic RNAs(ci RNAs) escaping from DBR1 debranching of intron lariats are co-transcriptionally produced from prem RNA splicing, but their turnover and mechanism of action have remained elusive. We report that RNase H1 degrades a subgroup of ci RNAs in human cells. Many ci RNAs contain high GC% and tend to form DNA:RNA hybrids(R-loops) for RNase H1 cleavage, a process that appears to promote Pol II transcriptional elongation at ci RNA-producing loci. One ci RNA, ciankrd52, shows a stronger ability of R-loop formation than that of its cognate pre-m RNA by maintaining a locally open RNA structure in vitro. This allows the release of pre-m RNA from R-loops by ci-ankrd52 replacement and subsequent ci RNA removal via RNase H1 for efficient transcriptional elongation. We propose that such an R-loop dependent ci RNA degradation likely represents a mechanism that on one hand limits ci RNA accumulation by recruiting RNase H1 and on the other hand resolves Rloops for transcriptional elongation at some GC-rich ci RNA-producing loci.
