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U4 spliceosomal RNA

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base pairing between the U6 snRNA in two highly conserved stem regions. It is suggested that this base-pairing interaction prevents the U6 snRNA from assembling with the U2 snRNA into the conformation required for catalytic activity. If the U4 snRNA is degraded and thereby removed from the spliceosome, splicing is effectively halted. The U4 and U6 snRNAs are demonstratively required for splicing in vitro.
251: 259: 172: 163: 40: 238:, involved with the U6 snRNA in the di-snRNP, as well as involved with both the U6 snRNA and the U5 snRNA in the tri-snRNP. The different formats have been proposed to coincide with different temporal events in the activity of the penta-snRNP, or as intermediates in the step-wise model of spliceosome assembly and activity. 278:
indicate that U4 snRNA secondary structure contains several conserved motifs, which serve structural as well as intermediary roles in establishing interactions with other splicing components. The putative U4/U6 snRNA base pairing secondary structure shown in Figure 2., is conserved across a diverse
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The U4 snRNA must be displaced from U6 snRNA in an ATP dependent process involving the protein Brr2 - before the spliceosome is made active. A cycle has been proposed including both Brr2 as well as the protein prp24 which selectively re-anneals U4 to the U6 snRNA. A ring of Sm proteins surround a
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The U4 snRNA (and its likely analog snR14 in Yeast) has been shown not to participate directly in the specific catalytic activities of the splicing reaction, and is proposed instead to act as a regulator of the U6 snRNA. The U4 snRNA inhibits spliceosome activity during assembly by complementary
992:
Mougin A, Gottschalk A, Fabrizio P, Lührmann R, Branlant C (April 2002). "Direct probing of RNA structure and RNA-protein interactions in purified HeLa cell's and yeast spliceosomal U4/U6.U5 tri-snRNP particles".
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conserved region of the U4 snRNA near the 3' end which are expected to promote favorable interactions between the different snRNPs as well as possibly protect the U4 snRNA from degradation by
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set of organisms suggesting the splicing machinery's ancient origins. It has been shown previously that a highly conserved Kinked-loop participates in specific protein interactions.
1030:"The trans-spliceosomal U4 RNA from the monogenetic trypanosomatid Leptomonas collosoma. Cloning and identification of a transcribed trna-like element that controls its expression" 643:
Siliciano PG, Brow DA, Roiha H, Guthrie C (August 1987). "An essential snRNA from S. cerevisiae has properties predicted for U4, including interaction with a U6-like snRNA".
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Madhani HD, Guthrie C (November 1992). "A novel base-pairing interaction between U2 and U6 snRNAs suggests a mechanism for the catalytic activation of the spliceosome".
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enzymes. Over 100 proteins have been identified that participate in spliceosomal pathway, several proteins of varying size are also known to interact with the U4 snRNP.
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Blencowe BJ, Sproat BS, Ryder U, Barabino S, Lamond AI (November 1989). "Antisense probing of the human U4/U6 snRNP with biotinylated 2'-OMe RNA oligonucleotides".
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Stark H, Dube P, Lührmann R, Kastner B (January 2001). "Arrangement of RNA and proteins in the spliceosomal U1 small nuclear ribonucleoprotein particle".
206:, and with each splicing round, it is displaced from the U6 snRNA (and the spliceosome) in an ATP-dependent manner, allowing U6 to re-fold and create the 816:
Berget SM, Robberson BL (August 1986). "U1, U2, and U4/U6 small nuclear ribonucleoproteins are required for in vitro splicing but not polyadenylation".
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Raghunathan PL, Guthrie C (February 1998). "A spliceosomal recycling factor that reanneals U4 and U6 small nuclear ribonucleoprotein particles".
418:"Evidence for the existence of snRNAs U4 and U6 in a single ribonucleoprotein complex and for their association by intermolecular base pairing" 234:
The U4 snRNA has been shown to exist in a number of different formats including: bound to proteins as a small nuclear Ribo-Nuclear Protein
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A 3D representation of a fragment of a U4 snRNA. The crystal structure of the spliceosomal 15.5KD protein is bound to a U4 snRNA fragment.
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The U4 snRNA secondary structure is suggested to alter depending on its interaction with the U6 snRNA. Several experiments involving
908:
Kambach C, Walke S, Nagai K (April 1999). "Structure and assembly of the spliceosomal small nuclear ribonucleoprotein particles".
516:"Biochemical and genetic analyses of the U5, U6, and U4/U6 x U5 small nuclear ribonucleoproteins from Saccharomyces cerevisiae" 691:"U4 small nuclear RNA dissociates from a yeast spliceosome and does not participate in the subsequent splicing reaction" 1647: 1291:"Evidence for a Prp24 binding site in U6 snRNA and in a putative intermediate in the annealing of U6 and U4 snRNAs" 1657: 275: 267: 49: 150: 1481:"Hierarchical, clustered protein interactions with U4/U6 snRNA: a biochemical role for U4/U6 proteins" 1340:"Specificity of Prp24 binding to RNA: a role for Prp24 in the dynamic interaction of U4 and U6 snRNAs" 1652: 1437: 1214: 467:"U5 small nuclear ribonucleoprotein: RNA structure analysis and ATP-dependent interaction with U4/U6" 1381:"Sm protein-Sm site RNA interactions within the inner ring of the spliceosomal snRNP core structure" 203: 45: 1461: 1184: 890: 841: 798: 668: 398: 1607: 1564: 1510: 1453: 1410: 1361: 1320: 1271: 1230: 1176: 1141: 1092: 1051: 1010: 974: 925: 882: 833: 790: 755: 720: 660: 625: 578: 537: 496: 447: 390: 349: 219: 195: 157: 145: 98: 369:"RNA unwinding in U4/U6 snRNPs requires ATP hydrolysis and the DEIH-box splicing factor Brr2" 1597: 1589: 1554: 1546: 1500: 1492: 1445: 1400: 1392: 1351: 1310: 1302: 1261: 1222: 1168: 1131: 1123: 1082: 1041: 1002: 964: 956: 917: 872: 825: 782: 747: 710: 702: 652: 615: 568: 527: 486: 478: 437: 429: 380: 339: 329: 109: 344: 214:
catalysis. A recycling process involving protein Brr2 releases U4 from U6, while protein
1441: 1218: 751: 1356: 1339: 1306: 1136: 1111: 599: 532: 515: 433: 184: 1602: 1577: 1559: 1534: 1505: 1480: 1405: 1380: 1315: 1290: 1250:"A stem/loop in U6 RNA defines a conformational switch required for pre-mRNA splicing" 969: 944: 921: 715: 690: 573: 556: 491: 466: 442: 417: 385: 368: 334: 317: 138: 135: 132: 129: 126: 1641: 1172: 877: 860: 829: 786: 656: 121: 1188: 845: 402: 1465: 894: 802: 672: 557:"Composition and functional characterization of the yeast spliceosomal penta-snRNP" 514:
Stevens SW, Barta I, Ge HY, Moore RE, Young MK, Lee TD, Abelson J (November 2001).
318:"Crystal structure of the spliceosomal 15.5kD protein bound to a U4 snRNA fragment" 211: 102: 861:"Pre-mRNA splicing in vitro requires intact U4/U6 small nuclear ribonucleoprotein" 555:
Stevens SW, Ryan DE, Ge HY, Moore RE, Young MK, Lee TD, Abelson J (January 2002).
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Comolli LR, Ulyanov NB, Soto AM, Marky LA, James TL, Gmeiner WH (October 2002).
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Bringmann P, Appel B, Rinke J, Reuter R, Theissen H, Lührmann R (June 1984).
1628: 1593: 258: 223: 114: 1550: 1514: 1496: 1457: 1414: 1145: 1096: 1055: 1046: 1029: 1014: 1006: 978: 929: 706: 582: 541: 353: 1611: 1568: 1365: 1324: 1275: 1234: 1180: 886: 837: 794: 759: 724: 664: 629: 500: 451: 394: 171: 1112:"Prp8p dissection reveals domain structure and protein interaction sites" 960: 620: 603: 482: 316:
Vidovic I, Nottrott S, Hartmuth K, Lührmann R, Ficner R (December 2000).
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Boon KL, Norman CM, Grainger RJ, Newman AJ, Beggs JD (February 2006).
1449: 39: 1071:"A simple principle to explain the evolution of pre-mRNA splicing" 289: 257: 249: 235: 215: 170: 76: 1632: 199: 94: 71: 271: 88: 1200: 1198: 262:
Figure 2. Putative U4/U6 base pairing secondary structure.
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Thomas, J; Lea K; Zucker-Aprison E; Blumenthal T (1990).
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Urlaub H, Raker VA, Kostka S, Lührmann R (January 2001).
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of U4 in complex with a binding protein has been solved.
945:"NMR structure of the 3' stem-loop from human U4 snRNA" 738:
Guthrie C, Patterson B (1988). "Spliceosomal snRNAs".
1578:"The spliceosomal snRNAs of Caenorhabditis elegans" 198:
involved in the splicing of pre-messenger RNA (pre-
156: 144: 120: 108: 87: 82: 70: 62: 57: 32: 1479:Nottrott S, Urlaub H, Lührmann R (October 2002). 1028:Li L, Otake LR, Xu Y, Michaeli S (January 2000). 254:Figure 1. Naked U4 putative secondary structure. 311: 309: 307: 305: 1338:Ghetti A, Company M, Abelson J (April 1995). 1248:Fortner DM, Troy RG, Brow DA (January 1994). 684: 682: 594: 592: 181:U4 small nuclear Ribo-Nucleic Acid (U4 snRNA) 8: 27:Non-coding RNA component of the spliceosome 38: 1601: 1558: 1504: 1404: 1355: 1314: 1289:Jandrositz A, Guthrie C (February 1995). 1265: 1135: 1086: 1045: 968: 876: 714: 619: 572: 531: 490: 441: 384: 343: 333: 1069:Izquierdo JM, Valcárcel J (July 2006). 367:Raghunathan PL, Guthrie C (July 1998). 301: 187:component of the major or U2-dependent 29: 7: 859:Black DL, Steitz JA (August 1986). 752:10.1146/annurev.ge.22.120188.002131 1307:10.1002/j.1460-2075.1995.tb07060.x 465:Black DL, Pinto AL (August 1989). 434:10.1002/j.1460-2075.1984.tb01977.x 25: 689:Yean SL, Lin RJ (November 1991). 604:"Spliceosome assembly in yeast" 345:11858/00-001M-0000-0012-F75C-F 1: 922:10.1016/S0959-440X(99)80032-3 602:, Abelson J (November 1987). 574:10.1016/S1097-2765(02)00436-7 386:10.1016/S0960-9822(07)00345-4 335:10.1016/S1097-2765(00)00131-3 1629:Page for U4 spliceosomal RNA 1227:10.1126/science.279.5352.857 1173:10.1016/0092-8674(89)90036-6 878:10.1016/0092-8674(86)90345-4 830:10.1016/0092-8674(86)90344-2 787:10.1016/0092-8674(92)90556-R 657:10.1016/0092-8674(87)90031-6 274:, and chemical modification 202:). It forms a duplex with 1674: 218:re-anneals U4 and U6. The 37: 910:Curr. Opin. Struct. Biol 1397:10.1093/emboj/20.1.187 1047:10.1074/jbc.275.4.2259 1007:10.1006/jmbi.2002.5451 707:10.1128/MCB.11.11.5571 263: 255: 176: 1594:10.1093/nar/18.9.2633 276:RNA structure probing 268:X-ray crystallography 261: 253: 174: 50:sequence conservation 1551:10.1093/nar/25.1.102 1497:10.1093/emboj/cdf544 621:10.1101/gad.1.9.1014 483:10.1128/MCB.9.8.3350 1535:"The uRNA database" 1442:2001Natur.409..539S 1267:10.1101/gad.8.2.221 1219:1998Sci...279..857R 1128:10.1261/rna.2281306 1088:10.1101/gad.1449106 46:secondary structure 33:U4 spliceosomal RNA 961:10.1093/nar/gkf560 264: 256: 177: 1648:Small nuclear RNA 1582:Nucleic Acids Res 1539:Nucleic Acids Res 1533:Zwieb, C (1997). 949:Nucleic Acids Res 220:crystal structure 196:molecular machine 169: 168: 16:(Redirected from 1665: 1615: 1605: 1588:(9): 2633–2642. 1572: 1562: 1519: 1518: 1508: 1476: 1470: 1469: 1450:10.1038/35054102 1436:(6819): 539–42. 1425: 1419: 1418: 1408: 1376: 1370: 1369: 1359: 1335: 1329: 1328: 1318: 1286: 1280: 1279: 1269: 1245: 1239: 1238: 1213:(5352): 857–60. 1202: 1193: 1192: 1156: 1150: 1149: 1139: 1107: 1101: 1100: 1090: 1066: 1060: 1059: 1049: 1025: 1019: 1018: 989: 983: 982: 972: 940: 934: 933: 905: 899: 898: 880: 856: 850: 849: 813: 807: 806: 770: 764: 763: 740:Annu. 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Cell 246:Structure 224:stem-loop 115:Eukaryota 110:Domain(s) 1515:12374753 1458:11206553 1415:11226169 1189:45969803 1146:16373487 1097:16818600 1056:10644672 1015:11955014 979:12384583 930:10322216 846:44660539 600:Cheng SC 583:11804584 542:11720284 403:14302377 354:11163207 222:of a 5′ 212:splicing 103:splicing 18:U4 snRNA 1612:2339054 1569:9016512 1466:4421636 1438:Bibcode 1366:7585243 1357:1369067 1325:7882985 1276:8299941 1235:9452384 1215:Bibcode 1207:Science 1181:2478298 1137:1370899 895:2899820 887:2427202 838:2427201 803:6407709 795:1423631 760:2977088 725:1833635 673:9476222 665:2440583 630:2962902 533:1370197 501:2552294 452:6204860 395:9705931 77:RF00015 1610:  1603:330746 1600:  1567:  1560:146409 1557:  1513:  1506:129076 1503:  1485:EMBO J 1464:  1456:  1430:Nature 1413:  1406:140196 1403:  1385:EMBO J 1364:  1354:  1323:  1316:398149 1313:  1295:EMBO J 1274:  1233:  1187:  1179:  1144:  1134:  1095:  1054:  1013:  977:  970:137124 967:  928:  893:  885:  844:  836:  801:  793:  758:  723:  716:361927 713:  671:  663:  628:  581:  540:  530:  499:  492:362380 489:  450:  443:557523 440:  422:EMBO J 401:  393:  352:  63:Symbol 1462:S2CID 1185:S2CID 891:S2CID 842:S2CID 799:S2CID 669:S2CID 399:S2CID 290:RNAse 236:snRNP 216:Prp24 183:is a 99:snRNA 52:of U4 1633:Rfam 1608:PMID 1565:PMID 1511:PMID 1454:PMID 1411:PMID 1362:PMID 1321:PMID 1272:PMID 1231:PMID 1177:PMID 1161:Cell 1142:PMID 1093:PMID 1052:PMID 1011:PMID 975:PMID 926:PMID 883:PMID 865:Cell 834:PMID 818:Cell 791:PMID 775:Cell 756:PMID 721:PMID 661:PMID 645:Cell 626:PMID 579:PMID 538:PMID 497:PMID 448:PMID 391:PMID 350:PMID 210:for 200:mRNA 191:– a 179:The 164:PDBe 95:Gene 91:type 72:Rfam 48:and 1631:at 1598:PMC 1590:doi 1555:PMC 1547:doi 1501:PMC 1493:doi 1446:doi 1434:409 1401:PMC 1393:doi 1352:PMC 1344:RNA 1311:PMC 1303:doi 1262:doi 1223:doi 1211:279 1169:doi 1132:PMC 1124:doi 1116:RNA 1083:doi 1042:doi 1038:275 1003:doi 999:317 965:PMC 957:doi 918:doi 873:doi 826:doi 783:doi 748:doi 711:PMC 703:doi 653:doi 616:doi 569:doi 528:PMC 520:RNA 487:PMC 479:doi 438:PMC 430:doi 381:doi 340:hdl 330:doi 272:NMR 158:PDB 89:RNA 1644:: 1606:. 1596:. 1586:18 1584:. 1580:. 1563:. 1553:. 1543:25 1541:. 1537:. 1509:. 1499:. 1489:21 1487:. 1483:. 1460:. 1452:. 1444:. 1432:. 1409:. 1399:. 1389:20 1387:. 1383:. 1360:. 1346:. 1342:. 1319:. 1309:. 1299:14 1297:. 1293:. 1270:. 1256:. 1252:. 1229:. 1221:. 1209:. 1197:^ 1183:. 1175:. 1165:59 1163:. 1140:. 1130:. 1120:12 1118:. 1114:. 1091:. 1079:20 1077:. 1073:. 1050:. 1036:. 1032:. 1009:. 997:. 973:. 963:. 953:30 951:. 947:. 924:. 912:. 889:. 881:. 869:46 867:. 863:. 840:. 832:. 822:46 820:. 797:. 789:. 779:71 777:. 754:. 744:22 742:. 719:. 709:. 699:11 697:. 693:. 681:^ 667:. 659:. 649:50 647:. 624:. 610:. 606:. 591:^ 577:. 563:. 559:. 536:. 522:. 518:. 495:. 485:. 473:. 469:. 446:. 436:. 424:. 420:. 397:. 389:. 375:. 371:. 348:. 338:. 324:. 320:. 304:^ 270:, 204:U6 146:SO 122:GO 101:; 97:; 66:U4 1614:. 1592:: 1571:. 1549:: 1517:. 1495:: 1468:. 1448:: 1440:: 1417:. 1395:: 1368:. 1348:1 1327:. 1305:: 1278:. 1264:: 1258:8 1237:. 1225:: 1217:: 1191:. 1171:: 1148:. 1126:: 1099:. 1085:: 1058:. 1044:: 1017:. 1005:: 981:. 959:: 932:. 920:: 914:9 897:. 875:: 848:. 828:: 805:. 785:: 762:. 750:: 727:. 705:: 675:. 655:: 632:. 618:: 612:1 585:. 571:: 565:9 544:. 524:7 503:. 481:: 475:9 454:. 432:: 426:3 405:. 383:: 377:8 356:. 342:: 332:: 326:6 20:)

Index

U4 snRNA

secondary structure
sequence conservation
Rfam
RF00015
RNA
Gene
snRNA
splicing
Domain(s)
Eukaryota
GO
GO:0017070
GO:0000353
GO:0000351
GO:0005687
GO:0046540
SO
SO:0000393
PDB
PDBe

non-coding RNA
spliceosome
eukaryotic
molecular machine
mRNA
U6
active site

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