In the fission yeast Schizosaccharomyces pombe,Mei2,an RNA-binding protein essential for entry into meiosis,regulates meiosis initiation.Mei2 binds to a specific non-coding RNA species,meiRNA,and accumulates at the sm...In the fission yeast Schizosaccharomyces pombe,Mei2,an RNA-binding protein essential for entry into meiosis,regulates meiosis initiation.Mei2 binds to a specific non-coding RNA species,meiRNA,and accumulates at the sme2 gene locus,which encodes meiRNA.Previous research has shown that the Mei2 C-terminal RNA recognition motif(RRM3)physically interacts with the meiRNA 5'region in vitro and stimulates meiosis in vivo.However,the underlying mechanisms still remain elusive.We first employed an in vitro crosslinking and immunoprecipitation sequencing(CLIP-seq)assay and demonstrated a preference for U-rich motifs of meiRNA by Mei2 RRM3.We then solved the crystal structures of Mei2 RRM3 in the apo form and complex with an 8 mer RNA fragment,derived from meiRNA,as detected by in vitro CLIP-seq.These results provide structural insights into the Mei2 RRM3-meiRNA complex and reveal that Mei2 RRM3 binds specifically to the Uuc(U)sequence.Furthermore,a structure-based Mei2 mutation,Mei2F644A causes defective karyogamy,suggesting an essential role of the RNA-binding ability of Mei2 in regulating meiosis.展开更多
AIM：To identify the expression of lens-related micro RNAs（miRNAs）in the central epithelium of transparent infant lenses and congenital cataract. METHODS：Lens-related mi RNAs were retrieved from Pub Med database. T...AIM：To identify the expression of lens-related micro RNAs（miRNAs）in the central epithelium of transparent infant lenses and congenital cataract. METHODS：Lens-related mi RNAs were retrieved from Pub Med database. The expression levels of these mi RNAs in transparent infant lenses and congenital cataract were determined by stem-loop reverse transcription-polymerase chain reaction（RT-PCR）. mi Randa algorithm was used to predict the target genes of these differentially expressed mi RNAs. The target m RNA was validated.RESULTS：Six lens-related mi RNAs were retrieved from screening Pub Med database. The most abundant mi RNA in transparent infant lenses according to stem-loop RT-PCR was mi R-184. miR-182 was up-regulated in congenital cataract. Contrarily,miR-204 and miR-124 was down-regulated.mi R-204 exhibited a more significant decrease in expression than mi R-124. In addition,Meis2 was predicted to be the target of mi R-204 using mi Randa algorithm. mi R-204mimic/antagomir transfection experiments suggested the negative correlation between the expression of mi R-204 and Meis2.CONCLUSION：The expression levels of miR-182,miR-204 and mi R-124 differ between the central epithelium of transparent infant lens and congenital cataract,suggesting their involvement in the pathogenesis of congenital cataract. miR-204 may act via silencing Meis2 to regulate lens development and congenital cataract formation.展开更多
The recent and exciting discovery of germline HOXB13 mutations in familial prostate cancer has brought HOX signaling to the forefront of prostate cancer research.An enhanced understanding of HOX signaling,and the co-f...The recent and exciting discovery of germline HOXB13 mutations in familial prostate cancer has brought HOX signaling to the forefront of prostate cancer research.An enhanced understanding of HOX signaling,and the co-factors regulating HOX protein specificity and transcriptional regulation,has the high potential to elucidate novel approaches to prevent,diagnose,stage,and treat prostate cancer.Toward our understanding of HOX biology in prostate development and prostate cancer,basic research in developmental model systems as well as other tumor sites provides a mechanistic framework to inform future studies in prostate biology.Here we describe our current understanding of HOX signaling in genitourinary development and cancer,current clinical data of HOXB13 mutations in multiple cancers including prostate cancer,and the role of HOX protein co-factors in development and cancer.These data highlight numerous gaps in our understanding of HOX function in the prostate,and present numerous potentially impactful mechanistic and clinical opportunities for future investigation.展开更多
基金This work was financially supported by grants from the Ministry of Science and Technology of China(2019YFA0508403)the Strategic Priority Research Program of the Chinese Academy of Sciences(XDB39010300)+2 种基金the National Natural Science Foundation of China(32090040,31870760,32171222,92149302,U1932122,and 32100958)the China Postdoctoral Science Foundation(2019M662182)the Fundamental Research Funds for the Central Universities(WK2340000097).
文摘In the fission yeast Schizosaccharomyces pombe,Mei2,an RNA-binding protein essential for entry into meiosis,regulates meiosis initiation.Mei2 binds to a specific non-coding RNA species,meiRNA,and accumulates at the sme2 gene locus,which encodes meiRNA.Previous research has shown that the Mei2 C-terminal RNA recognition motif(RRM3)physically interacts with the meiRNA 5'region in vitro and stimulates meiosis in vivo.However,the underlying mechanisms still remain elusive.We first employed an in vitro crosslinking and immunoprecipitation sequencing(CLIP-seq)assay and demonstrated a preference for U-rich motifs of meiRNA by Mei2 RRM3.We then solved the crystal structures of Mei2 RRM3 in the apo form and complex with an 8 mer RNA fragment,derived from meiRNA,as detected by in vitro CLIP-seq.These results provide structural insights into the Mei2 RRM3-meiRNA complex and reveal that Mei2 RRM3 binds specifically to the Uuc(U)sequence.Furthermore,a structure-based Mei2 mutation,Mei2F644A causes defective karyogamy,suggesting an essential role of the RNA-binding ability of Mei2 in regulating meiosis.
基金Supported by the Natural Science Foundation of China(No.81470614)the Fundamental Research Funds for the Central Universities sponsored by Xi’an Jiaotong University(No.xjj2013067)+1 种基金Youth Foundation of the First Affiliated Hospital,Medical College,Xi’an Jiaotong University(No.2014YK7)Scientific Research Funds for the Health and Family Planning of Shaanxi Province(No.2016D068)
文摘AIM：To identify the expression of lens-related micro RNAs（miRNAs）in the central epithelium of transparent infant lenses and congenital cataract. METHODS：Lens-related mi RNAs were retrieved from Pub Med database. The expression levels of these mi RNAs in transparent infant lenses and congenital cataract were determined by stem-loop reverse transcription-polymerase chain reaction（RT-PCR）. mi Randa algorithm was used to predict the target genes of these differentially expressed mi RNAs. The target m RNA was validated.RESULTS：Six lens-related mi RNAs were retrieved from screening Pub Med database. The most abundant mi RNA in transparent infant lenses according to stem-loop RT-PCR was mi R-184. miR-182 was up-regulated in congenital cataract. Contrarily,miR-204 and miR-124 was down-regulated.mi R-204 exhibited a more significant decrease in expression than mi R-124. In addition,Meis2 was predicted to be the target of mi R-204 using mi Randa algorithm. mi R-204mimic/antagomir transfection experiments suggested the negative correlation between the expression of mi R-204 and Meis2.CONCLUSION：The expression levels of miR-182,miR-204 and mi R-124 differ between the central epithelium of transparent infant lens and congenital cataract,suggesting their involvement in the pathogenesis of congenital cataract. miR-204 may act via silencing Meis2 to regulate lens development and congenital cataract formation.
基金DOD PCRP PC130587(Vander Griend)NWU/UC/NSUHS Prostate SPORE(P50 CA180995)the University of Chicago Comprehensive Cancer Center(UCCCC)+2 种基金especially the Cancer Center Support Grant(P30CA014599)H.Brechka and C.Van Opstall were supported by the Cancer Biology Training Grant(T32 CA009594)R.Bhanvadia is supported by a University of Chicago Pritzker School of Medicine Fellowship.
文摘The recent and exciting discovery of germline HOXB13 mutations in familial prostate cancer has brought HOX signaling to the forefront of prostate cancer research.An enhanced understanding of HOX signaling,and the co-factors regulating HOX protein specificity and transcriptional regulation,has the high potential to elucidate novel approaches to prevent,diagnose,stage,and treat prostate cancer.Toward our understanding of HOX biology in prostate development and prostate cancer,basic research in developmental model systems as well as other tumor sites provides a mechanistic framework to inform future studies in prostate biology.Here we describe our current understanding of HOX signaling in genitourinary development and cancer,current clinical data of HOXB13 mutations in multiple cancers including prostate cancer,and the role of HOX protein co-factors in development and cancer.These data highlight numerous gaps in our understanding of HOX function in the prostate,and present numerous potentially impactful mechanistic and clinical opportunities for future investigation.
