Epidermal growth factor receptor-tyrosine kinase inhibitors(EGFR-TKIs)positively affect the initial control of non-small cell lung cancer(NSCLC).Rapidly acquired resistance to EGFR-TKIs is a major hurdle in successful...Epidermal growth factor receptor-tyrosine kinase inhibitors(EGFR-TKIs)positively affect the initial control of non-small cell lung cancer(NSCLC).Rapidly acquired resistance to EGFR-TKIs is a major hurdle in successful treatment.However,the mechanisms that control the resistance of EGFR-TKIs remain largely unknown.RNA structures have widespread and crucial functions in many biological regulations;however,the functions of RNA structures in regulating cancer drug resistance remain unclear.Here,the psoralen analysis of RNA interactions and structures(PARIS)method is used to establish the higher-order RNA structure maps of EGFRTKIs-resistant and-sensitive cells of NSCLC.Our results show that RNA structural regions are enriched in untranslated regions(UTRs)and correlate with translation efficiency(TE).Moreover,yrdC N6-threonylcarbamoyltransferase domain containing(YRDC)promotes resistance to EGFR-TKIs.RNA structure formation in YRDC 30 UTR suppresses embryonic lethal abnormal vision-like 1(ELAVL1)binding,leading to EGFR-TKI sensitivity by impairing YRDC translation.A potential therapeutic strategy for cancer treatment is provided using antisense oligonucleotide(ASO)to perturb the interaction between RNA and protein.Our study reveals an unprecedented mechanism through which the RNA structure switch modulates EGFR-TKI resistance by controlling YRDC mRNA translation in an ELAVL1-dependent manner.展开更多
One of the most striking radiations in brachyuran evolution is the considerable morphological diversification of the external reproductive structures of primary freshwater crabs:the male first gonopod(G1)and the femal...One of the most striking radiations in brachyuran evolution is the considerable morphological diversification of the external reproductive structures of primary freshwater crabs:the male first gonopod(G1)and the female vulva(FV).However,the lack of quantitative studies,especially the lack of data on female genitalia,has seriously limited our understanding of genital evolution in these lineages.Here we examined 69 species of the large Chinese potamid freshwater crab genus Sinopotamon Bott,1967(more than 80%of the described species).We used a landmark-based geometric morphometric approach to analyze variation in the shape of the G1 and FV,and to compare the relative degree of variability of the genitalia with non-reproductive structures(the third maxillipeds).We found rapid divergent evolution of the genitalia among species of Sinopotamon when compared to non-reproductive traits.In addition,the reconstruction of ancestral groundplans,together with plotting analyses,indicated that the FV show the most rapid divergence,and that changes in FV traits correlate with changes in G1 traits.Here we provide new evidence for coevolution between the male and female external genitalia of Sinopotamon that has likely contributed to rapid divergent evolution and an associated burst of speciation in this lineage.展开更多
基金supported by grants from the Province and Ministry Coconstruction Major Program of Medical Science and Technique Foundation of Henan Province,China(Grant No.SBGJ202001007)the National Natural Science Foundation of China(Grant Nos.31870809 and 32121001)the Special Fund for Young and Middle School Leaders of Henan Health Commission,China(Grant No.HNSWJW-2020017).
文摘Epidermal growth factor receptor-tyrosine kinase inhibitors(EGFR-TKIs)positively affect the initial control of non-small cell lung cancer(NSCLC).Rapidly acquired resistance to EGFR-TKIs is a major hurdle in successful treatment.However,the mechanisms that control the resistance of EGFR-TKIs remain largely unknown.RNA structures have widespread and crucial functions in many biological regulations;however,the functions of RNA structures in regulating cancer drug resistance remain unclear.Here,the psoralen analysis of RNA interactions and structures(PARIS)method is used to establish the higher-order RNA structure maps of EGFRTKIs-resistant and-sensitive cells of NSCLC.Our results show that RNA structural regions are enriched in untranslated regions(UTRs)and correlate with translation efficiency(TE).Moreover,yrdC N6-threonylcarbamoyltransferase domain containing(YRDC)promotes resistance to EGFR-TKIs.RNA structure formation in YRDC 30 UTR suppresses embryonic lethal abnormal vision-like 1(ELAVL1)binding,leading to EGFR-TKI sensitivity by impairing YRDC translation.A potential therapeutic strategy for cancer treatment is provided using antisense oligonucleotide(ASO)to perturb the interaction between RNA and protein.Our study reveals an unprecedented mechanism through which the RNA structure switch modulates EGFR-TKI resistance by controlling YRDC mRNA translation in an ELAVL1-dependent manner.
基金This project received funding(to Hongying Sun)from the the National Natural Science Foundation of China(No.31471972 and 31772427).
文摘One of the most striking radiations in brachyuran evolution is the considerable morphological diversification of the external reproductive structures of primary freshwater crabs:the male first gonopod(G1)and the female vulva(FV).However,the lack of quantitative studies,especially the lack of data on female genitalia,has seriously limited our understanding of genital evolution in these lineages.Here we examined 69 species of the large Chinese potamid freshwater crab genus Sinopotamon Bott,1967(more than 80%of the described species).We used a landmark-based geometric morphometric approach to analyze variation in the shape of the G1 and FV,and to compare the relative degree of variability of the genitalia with non-reproductive structures(the third maxillipeds).We found rapid divergent evolution of the genitalia among species of Sinopotamon when compared to non-reproductive traits.In addition,the reconstruction of ancestral groundplans,together with plotting analyses,indicated that the FV show the most rapid divergence,and that changes in FV traits correlate with changes in G1 traits.Here we provide new evidence for coevolution between the male and female external genitalia of Sinopotamon that has likely contributed to rapid divergent evolution and an associated burst of speciation in this lineage.
