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The −10 position of the RNA is an important determinant of binding affinity for coat protein. Adenine at this position in other RNA stem-loops makes three hydrogen bonds to protein functional groups. Substituting 2AP for the −10 adenine in the F5 aptamer yields an RNA with the highest yet reported affinity for coat protein. The refined X-ray structure shows that the 2AP base makes an additional hydrogen bond to the protein compared to adenine that is presumably the principal origin of the increased affinity. There are also slight changes in phosphate backbone positions compared to unmodified F5 that probably also contribute to affinity. Such phosphate movements are common in structures of RNAs bound to the MS2 \u003Cjats:italic>T\u003C\u002Fjats:italic> = 3 protein shell and highlight problems for de novo design of RNA binding ligands.\u003C\u002Fjats:p>","\u003Cjats:p>Chúng tôi đã xác định cấu trúc của một aptamer RNA (F5), chứa 2′-deoxy-2-aminopurine (2AP) tại vị trí −10, kết hợp với protein vỏ MS2 bằng cách ngâm RNA vào các hạt MS2 đã được tinh thể hóa trước. Vị trí −10 của RNA là một yếu tố quan trọng quyết định ái lực liên kết với protein vỏ. Adenine tại vị trí này trong các cấu trúc RNA stem-loop khác tạo ra ba liên kết hydro với các nhóm chức năng của protein. Việc thay thế 2AP cho adenine tại vị trí −10 trong aptamer F5 tạo ra một RNA có ái lực cao nhất được báo cáo cho đến nay đối với protein vỏ. Cấu trúc X-ray đã tinh chỉnh cho thấy cơ sở 2AP tạo ra một liên kết hydro bổ sung với protein so với adenine, điều này có thể là nguồn gốc chính của sự gia tăng ái lực. Cũng có một số thay đổi nhỏ trong vị trí của xương phosphate so với F5 chưa được chỉnh sửa, điều này cũng có thể góp phần vào ái lực. 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All of the determined structures of aptamers in complex with small molecule targets show that aptamers cage such ligands. In structures of aptamers in complex with proteins that naturally bind nucleic acid, the aptamers occupy the nucleic acid binding site and often mimic the natural interactions. Here we present a crystal structure of an RNA aptamer bound to human thrombin, a protein that does not naturally bind nucleic acid, at 1.9 Å resolution. The aptamer, which adheres to thrombin at the binding site for heparin, presents an extended molecular surface that is complementary to the protein. Protein recognition involves the stacking of single-stranded adenine bases at the core of the tertiary fold with arginine side chains. 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Nhận diện protein liên quan đến việc chồng chất các gốc adenine đơn ở lõi của cấu trúc thứ cấp với các chuỗi bên arginine. 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Dev. Biol. Anim., 35, 533, 10.1007\u002Fs11626-999-0064-y",{"doi":1050},"10.1007\u002Fs11626-999-0064-y",{"id":23,"text":1052,"url":23,"identifiers":1053},"10.1038\u002F355564a0",{"doi":1052},{"id":23,"text":1055,"url":23,"identifiers":1056},"Bode,, 1992, The refined 1.9-Å X-ray crystal structure of D-Phe-Pro-Arg chloromethylketone-inhibited human α-thrombin: Structure analysis, overall structure, electrostatic properties, detailed active-site geometry, and structure–function relationships, Protein Sci., 1, 426, 10.1002\u002Fpro.5560010402",{"doi":1057},"10.1002\u002Fpro.5560010402",{"id":23,"text":1059,"url":23,"identifiers":1060},"Brünger, A.T. (1992) X-PLOR version 3.1: A system for X-ray crystallography and NMR (Yale University Press, New Haven, CT).",{},{"id":23,"text":1062,"url":23,"identifiers":1063},"10.1107\u002FS0907444998003254",{"doi":1062},{"id":23,"text":1065,"url":23,"identifiers":1066},"10.1016\u002FS0076-6879(97)77027-7",{"doi":1065},{"id":23,"text":1068,"url":23,"identifiers":1069},"10.1074\u002Fjbc.M411606200",{"doi":1068},{"id":23,"text":1071,"url":23,"identifiers":1072},"10.1126\u002Fscience.1084183",{"doi":1071},{"id":23,"text":1074,"url":23,"identifiers":1075},"1994, The CCP4 suite: Programs for X-ray crystallography, Acta Crystallogr., D50, 760",{},{"id":23,"text":751,"url":23,"identifiers":1077},{"doi":751},{"id":23,"text":1079,"url":23,"identifiers":1080},"10.1093\u002Fnar\u002Fgnf107",{"doi":1079},{"id":23,"text":1082,"url":23,"identifiers":1083},"10.1093\u002Fnar\u002F23.11.2019",{"doi":1082},{"id":23,"text":1085,"url":23,"identifiers":1086},"10.1038\u002Fnsmb810",{"doi":1085},{"id":23,"text":1088,"url":23,"identifiers":1089},"10.1378\u002Fchest.124.3_suppl.11S",{"doi":1088},{"id":23,"text":1091,"url":23,"identifiers":1092},"10.1126\u002Fscience.1083917",{"doi":1091},{"id":23,"text":435,"url":23,"identifiers":1094},{"doi":435},{"id":23,"text":1096,"url":23,"identifiers":1097},"Epa,, 2001, Shape and electrostatic complementarity at viral antigen–antibody complexes, Curr. 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Haemost., 85, 958, 10.1055\u002Fs-0037-1615947",{"doi":1117},"10.1055\u002Fs-0037-1615947",{"id":23,"text":1119,"url":23,"identifiers":1120},"10.1073\u002Fpnas.1632011100",{"doi":1119},{"id":23,"text":1122,"url":23,"identifiers":1123},"10.1038\u002Fnm1296-1386",{"doi":1122},{"id":23,"text":1125,"url":23,"identifiers":1126},"10.1093\u002Femboj\u002F17.15.4535",{"doi":1125},{"id":23,"text":1128,"url":23,"identifiers":1129},"10.1016\u002Fj.febslet.2004.04.087",{"doi":1128},{"id":23,"text":789,"url":23,"identifiers":1131},{"doi":789},{"id":23,"text":1133,"url":23,"identifiers":1134},"10.1021\u002Fja953943i",{"doi":1133},{"id":23,"text":1136,"url":23,"identifiers":1137},"10.1093\u002Fnar\u002F22.13.2619",{"doi":1136},{"id":23,"text":1139,"url":23,"identifiers":1140},"10.1006\u002Fviro.1997.8773",{"doi":1139},{"id":23,"text":1142,"url":23,"identifiers":1143},"10.1006\u002Fjmbi.1993.1648",{"doi":1142},{"id":23,"text":1145,"url":23,"identifiers":1146},"Lebruska,, 1999, Selection and characterization of an RNA decoy for transcription factor NF-κ B, Biochemistry, 38, 3168, 10.1021\u002Fbi982515x",{"doi":1147},"10.1021\u002Fbi982515x",{"id":23,"text":1149,"url":23,"identifiers":1150},"10.1073\u002Fpnas.0509069102",{"doi":1149},{"id":23,"text":1152,"url":23,"identifiers":1153},"10.1038\u002Fnsmb811",{"doi":1152},{"id":23,"text":1155,"url":23,"identifiers":1156},"10.1002\u002F1097-0134(20000815)40:3\u003C389::AID-PROT50>3.0.CO;2-2",{"doi":1155},{"id":23,"text":1158,"url":23,"identifiers":1159},"10.1073\u002Fpnas.90.8.3745",{"doi":1158},{"id":23,"text":1161,"url":23,"identifiers":1162},"10.1093\u002Fbioinformatics\u002Fbtl470",{"doi":1161},{"id":23,"text":1164,"url":23,"identifiers":1165},"Ng,, 2005, Targeting angiogenesis, the underlying disorder in neovascular age-related macular degeneration, Can. J. Ophthalmol., 40, 352, 10.1016\u002FS0008-4182(05)80078-X",{"doi":1166},"10.1016\u002FS0008-4182(05)80078-X",{"id":23,"text":1168,"url":23,"identifiers":1169},"Nicholls, A. (1992) GRASP: Graphical representation and analysis of surface properties (Columbia University Press, New York, NY).",{},{"id":23,"text":1171,"url":23,"identifiers":1172},"10.1146\u002Fannurev.med.56.062904.144915",{"doi":1171},{"id":23,"text":1174,"url":23,"identifiers":1175},"Nimjee, S.M. Oney, S. Volovyk, Z. Long, S.B. Hoffman, M. Sullenger, B. (2008) Synergistic effect of oligonucleotide ligands that inhibit exosites 1 and 2 on thrombin. RNA, (in press)..",{"doi":1176},"10.1261\u002Frna.1240109",{"id":23,"text":1178,"url":23,"identifiers":1179},"Olson,, 1991, Quantitative characterization of the thrombin–heparin interaction. Discrimination between specific and nonspecific binding models, J. Biol. Chem., 266, 6342, 10.1016\u002FS0021-9258(18)38124-9",{"doi":1180},"10.1016\u002FS0021-9258(18)38124-9",{"id":23,"text":1182,"url":23,"identifiers":1183},"10.1016\u002FS0076-6879(97)76066-X",{"doi":1182},{"id":23,"text":1185,"url":23,"identifiers":1186},"10.1107\u002FS0907444995013977",{"doi":1185},{"id":23,"text":1188,"url":23,"identifiers":1189},"Padmanabhan,, 1993, The structure of α-thrombin inhibited by a 15-mer single-stranded DNA aptamer, J. Biol. Chem., 268, 17651, 10.1016\u002FS0021-9258(17)46749-4",{"doi":1190},"10.1016\u002FS0021-9258(17)46749-4",{"id":23,"text":1192,"url":23,"identifiers":1193},"10.1126\u002Fscience.1857967",{"doi":1192},{"id":23,"text":1195,"url":23,"identifiers":1196},"Rau,, 2007, Serpins in thrombosis, hemostasis and fibrinolysis, J. Thromb. Haemost., 5, 102, 10.1111\u002Fj.1538-7836.2007.02516.x",{"doi":1197},"10.1111\u002Fj.1538-7836.2007.02516.x",{"id":23,"text":1199,"url":23,"identifiers":1200},"10.1261\u002Frna.657708",{"doi":1199},{"id":23,"text":1202,"url":23,"identifiers":1203},"10.1074\u002Fjbc.273.32.20556",{"doi":1202},{"id":23,"text":1205,"url":23,"identifiers":1206},"Rusconi,, 2002, RNA aptamers as reversible antagonists of coagulation factor IXa, Nature, 419, 90, 10.1038\u002Fnature00963",{"doi":1207},"10.1038\u002Fnature00963",{"id":23,"text":1209,"url":23,"identifiers":1210},"10.1006\u002Fjmbi.1994.1105",{"doi":1209},{"id":23,"text":1212,"url":23,"identifiers":1213},"10.1023\u002FA:1015346504499",{"doi":1212},{"id":23,"text":1215,"url":23,"identifiers":1216},"10.1016\u002FS0968-0004(00)88945-8",{"doi":1215},{"id":23,"text":1218,"url":23,"identifiers":1219},"10.1016\u002F0092-8674(90)90455-N",{"doi":1218},{"id":23,"text":1221,"url":23,"identifiers":1222},"10.1038\u002F71253",{"doi":1221},{"id":23,"text":1224,"url":23,"identifiers":1225},"10.1016\u002FS1074-5521(03)00024-3",{"doi":1224},{"id":23,"text":516,"url":23,"identifiers":1227},{"doi":516},{"id":23,"text":1229,"url":23,"identifiers":1230},"Wang,, 1993, A DNA aptamer which binds to and inhibits thrombin exhibits a new structural motif for DNA, Biochemistry, 32, 1899, 10.1021\u002Fbi00059a003",{"doi":1231},"10.1021\u002Fbi00059a003",{"id":23,"text":1233,"url":23,"identifiers":1234},"10.1006\u002Fmthe.2001.0495",{"doi":1233},{"id":23,"text":1236,"url":23,"identifiers":1237},"10.1006\u002Fjmbi.1998.2400",{"doi":1236},{"id":1239,"createTime":1240,"updateTime":1241,"relativeEntities":1242,"slug":1243,"properties":1244,"entityType":166,"verifyStatus":167,"verifyTime":1240,"verifyNote":169,"languages":1262,"translateLanguages":1263,"viewCount":24,"primaryUrl":1264,"fullTextUrl":23,"authors":1265,"publicationType":353,"publisherRelationship":1300,"citationCount":1349,"citationInfo":1350,"publishDate":1353,"publishYear":1351,"citationAnalyzeStatus":22,"lastCitationAnalyze":23,"indexDatabases":1354,"openAccess":23,"references":1355,"isForceReanalyzing":532},"0d1f97cb-2ea9-4634-9c47-5d568faaa8b6","2024-12-27T14:15:17.294+00:00","2025-02-21T14:07:55.822+00:00",[],"Human-mitochondrial-tRNA-sup-Met-sup-is-exported-to-the-cytoplasm-and-associates-with-the-Argonaute-2-protein",{"mag":1245,"keywords":1247,"pmc":1248,"openalex":1250,"abstract":1252,"title":1255,"pm":1258,"doi":1260},{"VOID":1246},"2026550718",{"VI":151},{"VOID":1249},"1370769",{"VOID":1251},"W2026550718",{"EN":1253,"VI":1254},"\u003Cjats:p>Argonaute (Ago) proteins are the effector proteins of RNA interference (RNAi) and related silencing mechanisms that are mediated by small RNAs. Ago proteins bind directly to microRNAs (miRNAs) and to short interfering RNAs and are the core protein components of RNA induced silencing complexes (RISCs) and microRNPs (miRNPs). Here we report that an ~70-nt RNA associates specifically with immunopurified Ago2 expressed in human 293 cells. By directional cloning we identified this RNA as the mitochondrial tRNA\u003Cjats:sup>Met\u003C\u002Fjats:sup> (mt tRNA\u003Cjats:sup>Met\u003C\u002Fjats:sup>). Various exported (mt) tRNAs were detected in the cytosol of 293 cells, but Ago2 was found selectively bound to (mt) tRNA\u003Cjats:sup>Met\u003C\u002Fjats:sup>. The association in the cytosol of exported (mt) tRNA\u003Cjats:sup>Met\u003C\u002Fjats:sup> with Ago2 complements genetic and microscopic data that link mitochondria with RNAi-related components and events.\u003C\u002Fjats:p>","\u003Cjats:p>Protein Argonaute (Ago) là các protein tác động của hiện tượng can thiệp RNA (RNAi) và các cơ chế kìm hãm liên quan được điều hòa bởi các RNA nhỏ. Các protein Ago liên kết trực tiếp với microRNA (miRNA) và với các RNA can thiệp ngắn, đồng thời là các thành phần protein lõi của các phức hợp kìm hãm RNA được tạo ra (RISCs) và microRNPs (miRNPs). Trong nghiên cứu này, chúng tôi báo cáo rằng một RNA khoảng 70 nucleotide liên kết cụ thể với Ago2 được tinh chế bằng miễn dịch và được biểu hiện trong tế bào 293 của người. Thông qua việc ghép nối theo hướng, chúng tôi đã xác định RNA này là tRNA\u003Cjats:sup>Met\u003C\u002Fjats:sup> của ti thể (mt tRNA\u003Cjats:sup>Met\u003C\u002Fjats:sup>). Nhiều tRNA (mt) khác nhau đã được phát hiện trong tế bào chất của tế bào 293, nhưng Ago2 chỉ được tìm thấy gắn kết có chọn lọc với (mt) tRNA\u003Cjats:sup>Met\u003C\u002Fjats:sup>. Sự liên kết trong tế bào chất của (mt) tRNA\u003Cjats:sup>Met\u003C\u002Fjats:sup> bị xuất khẩu với Ago2 phù hợp với các dữ liệu di truyền và vi thể liên kết ti thể với các thành phần và sự kiện liên quan đến RNAi.\u003C\u002Fjats:p>",{"EN":1256,"VI":1257},"Human mitochondrial tRNA\u003Csup>Met\u003C\u002Fsup> is exported to the cytoplasm and associates with the Argonaute 2 protein","tRNA\u003Csup>Met\u003C\u002Fsup> của ti thể người được xuất sang tế bào chất và kết hợp với protein Argonaute 2",{"VOID":1259},"15872185",{"VOID":1261},"10.1261\u002Frna.2210805",[171],[173],"http:\u002F\u002Frnajournal.cshlp.org\u002Flookup\u002Fdoi\u002F10.1261\u002Frna.2210805",[1266,1283],{"id":1267,"sortIndex":24,"researcher":23,"roles":1268,"affiliations":1269,"properties":1278,"displayName":1280,"givenName":23,"familyName":23},"fcf5bedd-e459-45a2-8022-b0639a1afeeb",[],[1270],{"id":1271,"sortIndex":24,"affiliation":1272,"properties":23},"9060b621-0f2d-4f64-add0-2fca6944df07",{"id":1271,"createTime":23,"updateTime":23,"relativeEntities":1273,"slug":23,"properties":1274,"entityType":23,"verifyStatus":23,"verifyTime":23,"verifyNote":23,"languages":23,"translateLanguages":23,"viewCount":23,"url":23,"parentIds":1277,"statistic":23},[],{"title":1275},{"VI":1276},"Department of Pathology and Laboratory Medicine (Division of Neuropathology), University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104 USA",[],{"title":1279,"openalex":1281},{"EN":1280},"Elisavet Maniataki",{"VOID":1282},"A5074999929",{"id":1284,"sortIndex":99,"researcher":23,"roles":1285,"affiliations":1286,"properties":1293,"displayName":1297,"givenName":23,"familyName":23},"bb51c043-11d0-4d67-b2b0-9680e5cba906",[],[1287],{"id":1271,"sortIndex":24,"affiliation":1288,"properties":23},{"id":1271,"createTime":23,"updateTime":23,"relativeEntities":1289,"slug":23,"properties":1290,"entityType":23,"verifyStatus":23,"verifyTime":23,"verifyNote":23,"languages":23,"translateLanguages":23,"viewCount":23,"url":23,"parentIds":1292,"statistic":23},[],{"title":1291},{"VI":1276},[],{"orcid":1294,"title":1296,"openalex":1298},{"VOID":1295},"https:\u002F\u002Forcid.org\u002F0000-0002-9852-1845",{"EN":1297},"Zissimos P. 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Here, the silkworm transcriptome was analyzed by RNA-seq. We identified 320 novel genes, modified 1140 gene models, and found thousands of alternative splicing and 58 \u003Cjats:italic>trans\u003C\u002Fjats:italic>-splicing events. Studies of three SR proteins show that both their alternative splicing patterns and mRNA products are conserved from insect to human, and one isoform of Srsf6 with a retained intron is expressed sex-specifically in silkworm gonads. \u003Cjats:italic>Trans\u003C\u002Fjats:italic>-splicing of \u003Cjats:italic>mod(mdg4)\u003C\u002Fjats:italic> in silkworm was experimentally confirmed. We identified integrations from a common 5′-gene with 46 newly identified alternative 3′-exons that are located on both DNA strands over a 500-kb region. Other \u003Cjats:italic>trans\u003C\u002Fjats:italic>-splicing events in \u003Cjats:italic>B. mori\u003C\u002Fjats:italic> were predicted by bioinformatic analysis, in which 12 events were confirmed by RT-PCR, six events were further validated by chimeric SNPs, and two events were confirmed by allele-specific RT-PCR in F\u003Cjats:sub>1\u003C\u002Fjats:sub> hybrids from distinct silkworm lines of JS and L10, indicating that \u003Cjats:italic>trans\u003C\u002Fjats:italic>-splicing is more widespread in insects than previously thought. Analysis of the \u003Cjats:italic>B. mori\u003C\u002Fjats:italic> transcriptome by RNA-seq provides valuable information of regulatory alternative splicing events. The conservation of splicing events across species and newly identified \u003Cjats:italic>trans\u003C\u002Fjats:italic>-splicing events suggest that \u003Cjats:italic>B. mori\u003C\u002Fjats:italic> is a good model for future studies.\u003C\u002Fjats:p>","\u003Cjats:p>Các sự kiện cắt ghép thay thế và cắt ghép nối \u003Cjats:italic>trans\u003C\u002Fjats:italic> chưa được nghiên cứu hệ thống trong tằm \u003Cjats:italic>Bombyx mori\u003C\u002Fjats:italic>. Ở đây, hệ gen của tằm đã được phân tích bằng RNA-seq. Chúng tôi đã xác định được 320 gen mới, chỉnh sửa 1140 mô hình gen, và phát hiện hàng ngàn sự kiện cắt ghép thay thế và 58 sự kiện cắt ghép nối \u003Cjats:italic>trans\u003C\u002Fjats:italic>. Nghiên cứu ba protein SR cho thấy cả mẫu cắt ghép thay thế và sản phẩm mRNA của chúng đều được bảo tồn từ côn trùng đến người, và một isoform của Srsf6 với intron được giữ lại được biểu hiện theo giới tính cụ thể trong bộ sinh dục tằm. Sự kiện cắt ghép nối \u003Cjats:italic>mod(mdg4)\u003C\u002Fjats:italic> ở tằm đã được xác nhận qua thực nghiệm. Chúng tôi đã xác định được các tích hợp từ một gen 5′ chung với 46 exon 3′ thay thế mới được xác định nằm trên cả hai sợi DNA trong một khu vực 500-kb. Các sự kiện cắt ghép nối \u003Cjats:italic>trans\u003C\u002Fjats:italic> khác ở \u003Cjats:italic>B. mori\u003C\u002Fjats:italic> đã được dự đoán qua phân tích tin sinh học, trong đó 12 sự kiện được xác nhận qua RT-PCR, sáu sự kiện được xác nhận thêm bằng SNP chimeric, và hai sự kiện được xác nhận qua RT-PCR đặc hiệu allele trong các tổ hợp F\u003Cjats:sub>1\u003C\u002Fjats:sub> từ các dòng tằm khác nhau của JS và L10, cho thấy rằng \u003Cjats:italic>trans\u003C\u002Fjats:italic>-splicing phổ biến hơn trong côn trùng so với những gì được nghĩ trước đây. Phân tích hệ gen của \u003Cjats:italic>B. mori\u003C\u002Fjats:italic> bằng RNA-seq cung cấp thông tin quý giá về các sự kiện cắt ghép thay thế điều hòa. Sự bảo tồn của các sự kiện cắt ghép qua các loài và các sự kiện cắt ghép nối \u003Cjats:italic>trans\u003C\u002Fjats:italic> mới được xác định gợi ý rằng \u003Cjats:italic>B. mori\u003C\u002Fjats:italic> là một mô hình tốt cho các nghiên cứu trong tương lai.\u003C\u002Fjats:p>",{"EN":1433,"VI":1434},"Alternative splicing and \u003Ci>trans\u003C\u002Fi>-splicing events revealed by analysis of the \u003Ci>Bombyx mori\u003C\u002Fi> transcriptome","Các sự kiện cắt ghép thay thế và cắt ghép nối đã được tiết lộ bởi việc phân tích hệ gen của \u003Ci>Bombyx 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microRNA (miRNA) “sponge” method was introduced three years ago as a means to create continuous miRNA loss of function in cell lines and transgenic organisms. Sponge RNAs contain complementary binding sites to a miRNA of interest, and are produced from transgenes within cells. As with most miRNA target genes, a sponge's binding sites are specific to the miRNA seed region, which allows them to block a whole family of related miRNAs. This transgenic approach has proven to be a useful tool to probe miRNA functions in a variety of experimental systems. Here we will discuss the ways sponge and related constructs can be optimized and review recent applications of this method with particular emphasis on stable expression in cancer studies and in transgenic animals.\u003C\u002Fjats:p>","\u003Cjats:p>Phương pháp \"bã miRNA\" đã được giới thiệu ba năm trước như một cách để tạo ra sự mất chức năng miRNA liên tục trong các dòng tế bào và các sinh vật chuyển gen. RNA bã chứa các vị trí gắn kết bổ sung với miRNA mà chúng ta quan tâm, và được sản xuất từ các gen chuyển trong các tế bào. Cũng giống như hầu hết các gen mục tiêu miRNA, các vị trí gắn kết của một bã rất đặc hiệu với vùng hạt giống của miRNA, cho phép chúng chặn lại cả một gia đình miRNA liên quan. Cách tiếp cận chuyển gen này đã chứng tỏ là một công cụ hữu ích để khám phá chức năng của miRNA trong nhiều hệ thống thí nghiệm khác nhau. 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Despite the high degree of conservation of miRNAs, their functions in general, and in mammals particularly, are just beginning to be defined. Here we show that an oligonucleotide DNA array can be successfully used for the simultaneous analysis of miRNA expression profiles from tissues or cells. From a subset of miRNAs expressed in the brain we designed an oligonucleotide array spotted with probes specific for 44 mature miRNAs. These arrays demonstrated precise regulation of miRNA expression at mammalian brain developmental epochs. About 20% of the probed miRNAs changed significantly in their expression during normal brain development, and two of them, miR-9 and miR-131, were dysregulated in presenilin-1 null mice exhibiting severe brain developmental defects. Transcripts with regulated expression patterns on the arrays were validated by Northern blots. Additionally, a bioinformatic analysis of developmentally regulated miRNAs suggested potential mRNA targets. The arrays also revealed miRNAs distributed to translating polyribosomes in primary neurons where they are likely to modulate translation. Therefore, oligonucleotide arrays provide a new tool for studying miRNA expression in a variety of biological and pathobiological settings. Creating clusters of coexpressed miRNAs will contribute to understanding their regulation, functions, and discovery of mRNA targets.\u003C\u002Fjats:p>","\u003Cjats:p> Gần đây, hàng trăm microRNA (miRNA) đã được nhân bản từ nhiều loại sinh vật khác nhau trên toàn bộ hệ sinh thái. Mặc dù miRNA có mức độ bảo tồn cao, chức năng của chúng nói chung, và đặc biệt là ở động vật có vú, vẫn chỉ mới bắt đầu được xác định. Ở đây, chúng tôi cho thấy rằng một mảng DNA oligonucleotide có thể được sử dụng thành công để phân tích song song các hồ sơ biểu hiện miRNA từ mô hoặc tế bào. Từ một tập hợp con các miRNA thể hiện trong não, chúng tôi đã thiết kế một mảng oligonucleotide với các mồi đặc hiệu cho 44 miRNA trưởng thành. Những mảng này cho thấy sự điều chỉnh chính xác của biểu hiện miRNA trong các giai đoạn phát triển não của động vật có vú. Khoảng 20% số miRNA đã được kiểm tra có sự thay đổi đáng kể trong biểu hiện trong quá trình phát triển não bình thường, và hai trong số đó, miR-9 và miR-131, đã bị điều chỉnh bất thường ở chuột thiếu presenilin-1, những con chuột này có những khiếm khuyết nghiêm trọng trong phát triển não. Các bản sao có mẫu biểu hiện được điều chỉnh trên mảng đã được xác nhận bằng các bản Northern blot. Thêm vào đó, một phân tích sinh tin học của các miRNA được điều chỉnh theo phát triển đã gợi ý các mục tiêu mRNA tiềm năng. Các mảng cũng tiết lộ miRNA phân bố đến các polyribosome đang dịch mã trong các neuron nguyên phát, nơi chúng có thể điều chỉnh quá trình dịch mã. Do đó, các mảng oligonucleotide cung cấp một công cụ mới để nghiên cứu biểu hiện miRNA trong một loạt các bối cảnh sinh học và bệnh lý. Việc tạo ra các cụm của các miRNA đồng biểu hiện sẽ góp phần vào việc hiểu rõ hơn về sự điều chỉnh, chức năng của chúng, và phát hiện các mục tiêu mRNA.",{"EN":2458,"VI":2459},"A microRNA array reveals extensive regulation of microRNAs during brain development","Một mảng microRNA tiết lộ sự điều chỉnh rộng rãi của microRNA trong quá trình phát triển não",{"VOID":2461},"13130141",{"VOID":2022},[171],[173],"http:\u002F\u002Frnajournal.cshlp.org\u002Flookup\u002Fdoi\u002F10.1261\u002Frna.5980303",[2467,2486,2503,2518,2537],{"id":2468,"sortIndex":24,"researcher":23,"roles":2469,"affiliations":2470,"properties":2479,"displayName":2483,"givenName":23,"familyName":23},"8b5ff332-1353-470a-aab3-0fc814cf7e49",[],[2471],{"id":2472,"sortIndex":24,"affiliation":2473,"properties":23},"a2273bdb-f253-441a-b395-c2746512be5a",{"id":2472,"createTime":23,"updateTime":23,"relativeEntities":2474,"slug":23,"properties":2475,"entityType":23,"verifyStatus":23,"verifyTime":23,"verifyNote":23,"languages":23,"translateLanguages":23,"viewCount":23,"url":23,"parentIds":2478,"statistic":23},[],{"title":2476},{"VI":2477},"Center For Neurologic Diseases Brigham and Women's Hospital and Harvard Medical School Boston, Massachusetts 02115, USA",[],{"orcid":2480,"title":2482,"openalex":2484},{"VOID":2481},"https:\u002F\u002Forcid.org\u002F0000-0002-5080-5507",{"EN":2483},"Anna M. 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Brain Res., 61, 105",{},{"id":23,"text":2090,"url":23,"identifiers":2697},{"doi":2090},{"id":23,"text":2699,"url":23,"identifiers":2700},"10.1016\u002FS0092-8674(02)00863-2",{"doi":2699},{"id":23,"text":2702,"url":23,"identifiers":2703},"10.1016\u002FS0092-8674(00)80244-5",{"doi":2702},{"id":23,"text":2705,"url":23,"identifiers":2706},"10.1016\u002FS0959-437X(02)00318-0",{"doi":2705},{"id":23,"text":2708,"url":23,"identifiers":2709},"10.1016\u002FS1097-2765(00)80245-2",{"doi":2708},{"id":23,"text":2119,"url":23,"identifiers":2711},{"doi":2119},{"id":23,"text":2713,"url":23,"identifiers":2714},"10.1073\u002Fpnas.96.8.4650",{"doi":2713},{"id":2716,"createTime":2717,"updateTime":2718,"relativeEntities":2719,"slug":2720,"properties":2721,"entityType":166,"verifyStatus":167,"verifyTime":2717,"verifyNote":169,"languages":2739,"translateLanguages":2740,"viewCount":24,"primaryUrl":2741,"fullTextUrl":23,"authors":2742,"publicationType":353,"publisherRelationship":2779,"citationCount":117,"citationInfo":2829,"publishDate":2841,"publishYear":2830,"citationAnalyzeStatus":22,"lastCitationAnalyze":23,"indexDatabases":2842,"openAccess":23,"references":2843,"isForceReanalyzing":532},"14077a71-d782-4b05-b919-350da921f72e","2024-09-27T16:56:06.406+00:00","2025-02-17T23:11:55.870+00:00",[],"Circular-RNAs-diversity-of-form-and-function",{"mag":2722,"keywords":2724,"pmc":2725,"openalex":2727,"abstract":2729,"title":2732,"pm":2735,"doi":2737},{"VOID":2723},"2137691989",{"VI":151},{"VOID":2726},"4238349",{"VOID":2728},"W2137691989",{"EN":2730,"VI":2731},"\u003Cjats:p>It is now clear that there is a diversity of circular RNAs in biological systems. Circular RNAs can be produced by the direct ligation of 5′ and 3′ ends of linear RNAs, as intermediates in RNA processing reactions, or by “backsplicing,” wherein a downstream 5′ splice site (splice donor) is joined to an upstream 3′ splice site (splice acceptor). Circular RNAs have unique properties including the potential for rolling circle amplification of RNA, the ability to rearrange the order of genomic information, protection from exonucleases, and constraints on RNA folding. Circular RNAs can function as templates for viroid and viral replication, as intermediates in RNA processing reactions, as regulators of transcription in \u003Cjats:italic>cis\u003C\u002Fjats:italic>, as snoRNAs, and as miRNA sponges. Herein, we review the breadth of circular RNAs, their biogenesis and metabolism, and their known and anticipated functions.\u003C\u002Fjats:p>","\u003Cjats:p>Hiện nay, đã rõ rằng có một sự đa dạng của các RNA vòng trong các hệ thống sinh học. RNA vòng có thể được sản xuất bằng việc nối trực tiếp các đầu 5′ và 3′ của RNA thẳng, như những trung gian trong các phản ứng xử lý RNA, hoặc thông qua quá trình \"gập nối ngược\", trong đó một vị trí nối 5′ ở phía hạ lưu (người hiến nối) được kết hợp với một vị trí nối 3′ ở phía thượng lưu (người chấp nhận nối). RNA vòng có những tính chất độc đáo bao gồm tiềm năng cho quá trình khuếch đại vòng RNA, khả năng sắp xếp lại thứ tự của thông tin di truyền, bảo vệ khỏi các exonuclease, và hạn chế trong việc gập RNA. RNA vòng có thể hoạt động như các khuôn mẫu cho sự sao chép của viroid và virus, như những trung gian trong các phản ứng xử lý RNA, như các chất điều tiết phiên mã trong \u003Cjats:italic>cis\u003C\u002Fjats:italic>, như snoRNA, và như các miRNA hấp thụ. Ở đây, chúng tôi xem xét sự đa dạng của RNA vòng, sự hình thành và chuyển hóa của chúng, và các chức năng đã biết và dự đoán của chúng.\u003C\u002Fjats:p>",{"EN":2733,"VI":2734},"Circular RNAs: diversity of form and function","RNA Vòng: Đa dạng về hình thức và chức 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