pre-miRNA Information
pre-miRNA hsa-mir-4747   
Genomic Coordinates chr19: 4932687 - 4932740
Description Homo sapiens miR-4747 stem-loop
Comment None
RNA Secondary Structure

Mature miRNA Information
Mature miRNA hsa-miR-4747-5p
Sequence 1| AGGGAAGGAGGCUUGGUCUUAG |22
Evidence Experimental
Experiments Illumina
SNPs in miRNA
Mutant ID Mutant Position Mutant Source
rs560927363 4 dbSNP
rs1471226927 10 dbSNP
rs763137545 12 dbSNP
rs767337154 15 dbSNP
rs775298039 16 dbSNP
rs760472311 19 dbSNP
rs1207950315 21 dbSNP
Putative Targets

miRNA Expression profile
Human miRNA Tissue Atlas
Circulating MicroRNA Expression Profiling
Gene Information
Gene Symbol ZNF689   
Synonyms TIPUH1
Description zinc finger protein 689
Transcript NM_138447   
Expression
Putative miRNA Targets on ZNF689
3'UTR of ZNF689
(miRNA target sites are highlighted)
>ZNF689|NM_138447|3'UTR
   1 AAGGGGAAGGACTGCCTACGTTCATTTCATTTTATGGAGGGTCCCAGAAAAGGGAAGGAGGAGCCCCAGGTCATACAGGG
  81 CAGAGTCAGAACTAAACCCGGGTCTCCTGCTGCACAGAGCTGAACTTTGTATCTTGCAATGCGCTGGCTGCCTCCCTGTG
 161 CGTGTCTGGAACAGTCCCATTAGGAGAGGTGACGTCATTTGCTTAAAGTTTTCCAAGCTACCCTATCCTAAAATAGTTTG
 241 TGTGGATATCAGGGCTAAAAGTTCTCCCCATCTATTTTAGGGGCTGTCTGCTTTTCTAGTCTGTCCACACAGGGATTACC
 321 TGTCATCTTGCATGCAATCAGGAGAATCTCATAGGGGCAGGACCTTCCCCTACTCTGCCTCTTCCTCCATACTAGGTTGG
 401 AAAAATCTGGTTTAGCCCACTTTTTGCAACACTCCTGCCAAGTGGTCTTCTACCCATTGCTTGAAAATCTCTCTTGACAG
 481 GGAGCTCACTACCTCACAAGGCAGGTCATTTCATTGTGGGATCTATAGAAGGTTAAGTACCACATTCTCCTCTAAACCTT
 561 GCCTACGACATGTTTAATACTTCATCTACATAGCAGCCCTTCAGATAATCACAACCACTTTGCCCCCAAGTTTTCAGGTT
 641 AAGTAGCATGAATTTGGTCATTCCTTAAAGACAGGGTTTCAATTTCCACACATGATCTCTGCAAACAGGCACTGGGTTTT
 721 CAGTGTCCTTTTTGAAGGGTCATATAAAAATAAGGTAACACCACAGTGCCACTACACCTTCTGGGGCTGGACTTGTTTCA
 801 GCAGCTTTGGTTGCACTGAATTTGGGGGAGCTGCATGGTACCAGGGGTTTATTGGGTTGCAGATATATAAATGCCCTAAA
 881 CTTAAAAAAAAAAAAAAAAGCTATAAAACTAAGTCTTCATCTTGTATTTGGAAAATTGGTTCAAGCTGGGTATGAGACAT
 961 AAGTGTAGTCAGCTCTGGGAGAAGGTTGCTCTTAAGGAGAAGCAGGGACCTGTGGTTTAGCAGCAGGAAGTGCAAATGGG
1041 ACTGGCTTGTGCTCTACCTGGCAGACCTGGATTGGCTTCAGGCAGCCAGTGCCTGGAAAAGCCTGGAGAATTGGGCCGTA
1121 CTTGACCCTGATTCTCATCAGGCACAGATGAATCACAGGCACCTAAGAATCGGCACAGAACTTCCATGAGGCCTCAGTCA
1201 GCATTTTTTCACAAAATGAGCTGAGGCCATTCAAGGAGGCTAGAAAGAGGGAACTGAATCCAGAGAGGAAGAGTCTATAG
1281 TCATCAAGTTGTATCCATGCCAGCCTCCCTCCACAGAGGTGGCAGCAGCGTGGCTCAATCTGATCCACCTCCATGGCACC
1361 CACTGGGTAGGTGCTTCATAAAGCTTTACCGAGTTAAATGTGAACAAGGCCTACCACTTTGCCTTGGGCAGCTGCACCAA
1441 ATTAGAATTTCCAGATGTGACTCATCTCATATTCCAACAGCTGGAGTGGGTCATCCTTTACCCCTGTGGCTCCTTCCTAC
1521 AGCTCTCCTGATCTCAGCACAAGCAGGGGAGCAGCTGGGGGAACACAGCTTTATGTAATTACCTCTGTTCAATATTTAGC
1601 AAGTTGCATTGTAACATTGTAACTGTTTGTTTCTCCTTGGATGATGAGCTACCCCCAAGAAGGGGTCATATCAGATTGGG
1681 TCTCATTAAAATGTCTGATGAATGAAAAAAAAAAAAA
Target sites Provided by authors   Predicted by miRanda    DRVs    SNPs    DRVs & SNPs
miRNA-target interactions
(Predicted by miRanda)
ID Duplex structure Position Score MFE
1
miRNA  3' gaUUCUGGUUCGGAGGAAGGGa 5'
            |:|: ||:|   ||||||| 
Target 5' atAGGGGCAGG--ACCTTCCCc 3'
351 - 370 152.00 -21.40
2
miRNA  3' gauucuGGUUCGGAGGAAGGGa 5'
                |:: | ||||||||: 
Target 5' ttacccCTGTGGCTCCTTCCTa 3'
1498 - 1519 140.00 -16.00
3
miRNA  3' gaUUCUGGUUC--GGAGGAAGGGa 5'
            |||:::|||  || | |||:| 
Target 5' agAAGGTTAAGTACCACATTCTCc 3'
527 - 550 122.00 -13.30
DRVs in gene 3'UTRs
Mutant ID Mutant Position Mutant Source
COSN30101350 27 COSMIC
COSN30538564 30 COSMIC
COSN21528418 129 COSMIC
COSN9645489 131 COSMIC
COSN31964900 151 COSMIC
COSN20078629 156 COSMIC
COSN20065723 162 COSMIC
COSN31606159 195 COSMIC
COSN30176369 300 COSMIC
COSN31533695 323 COSMIC
COSN31556349 368 COSMIC
COSN20078630 490 COSMIC
COSN1185258 690 COSMIC
COSN32061441 884 COSMIC
COSN23782931 959 COSMIC
COSN32062584 1477 COSMIC
SNPs in gene 3'UTRs
Mutant ID Mutant Position Mutant Source
rs1370823081 2 dbSNP
rs1327174800 6 dbSNP
rs1443127230 7 dbSNP
rs542426608 11 dbSNP
rs749189576 16 dbSNP
rs1462678887 18 dbSNP
rs1375070033 19 dbSNP
rs773194504 20 dbSNP
rs370031295 33 dbSNP
rs769523291 35 dbSNP
rs117929446 40 dbSNP
rs1477045530 42 dbSNP
rs781440592 52 dbSNP
rs755177525 54 dbSNP
rs747305879 55 dbSNP
rs1465296423 61 dbSNP
rs1329781201 62 dbSNP
rs892834863 63 dbSNP
rs766968713 68 dbSNP
rs746674871 70 dbSNP
rs1231443536 73 dbSNP
rs1347633343 74 dbSNP
rs779968794 78 dbSNP
rs1237101247 81 dbSNP
rs1402883415 82 dbSNP
rs758620343 85 dbSNP
rs563600502 88 dbSNP
rs758859682 89 dbSNP
rs1392044604 94 dbSNP
rs1398841905 95 dbSNP
rs1301341236 96 dbSNP
rs1465328858 98 dbSNP
rs184155588 99 dbSNP
rs562023799 100 dbSNP
rs577606801 102 dbSNP
rs931754405 106 dbSNP
rs1443087649 107 dbSNP
rs148623506 108 dbSNP
rs754185087 109 dbSNP
rs767145699 111 dbSNP
rs773889115 114 dbSNP
rs759085105 115 dbSNP
rs1281464275 120 dbSNP
rs756488360 122 dbSNP
rs1213551979 126 dbSNP
rs753161599 127 dbSNP
rs191537720 128 dbSNP
rs1049823742 129 dbSNP
rs1040117157 133 dbSNP
rs996517709 137 dbSNP
rs774090803 139 dbSNP
rs765862960 141 dbSNP
rs541155716 142 dbSNP
rs773070167 143 dbSNP
rs769758646 145 dbSNP
rs1314482308 148 dbSNP
rs1417633636 150 dbSNP
rs1462762362 150 dbSNP
rs1384077699 152 dbSNP
rs1159097247 153 dbSNP
rs1470856564 154 dbSNP
rs907667222 155 dbSNP
rs1186285656 161 dbSNP
rs747889869 162 dbSNP
rs985148978 170 dbSNP
rs1388996635 177 dbSNP
rs573460470 185 dbSNP
rs776106891 186 dbSNP
rs1213395058 187 dbSNP
rs1303281490 188 dbSNP
rs916597255 190 dbSNP
rs1487525484 193 dbSNP
rs1284139941 194 dbSNP
rs776268453 196 dbSNP
rs1279630243 201 dbSNP
rs866294007 208 dbSNP
rs1353537630 212 dbSNP
rs765990251 213 dbSNP
rs960669975 213 dbSNP
rs555167372 225 dbSNP
rs768536598 226 dbSNP
rs747193883 228 dbSNP
rs1356259713 234 dbSNP
rs540002761 240 dbSNP
rs886911573 245 dbSNP
rs1295358164 246 dbSNP
rs1358437551 248 dbSNP
rs1397850754 253 dbSNP
rs1035081257 256 dbSNP
rs1048221965 257 dbSNP
rs930681229 267 dbSNP
rs780380095 270 dbSNP
rs147796088 272 dbSNP
rs750788932 274 dbSNP
rs1159804053 277 dbSNP
rs1011611968 280 dbSNP
rs1461522277 283 dbSNP
rs1419508893 284 dbSNP
rs1191104460 285 dbSNP
rs890033019 286 dbSNP
rs767977078 288 dbSNP
rs569526488 289 dbSNP
rs1415319005 294 dbSNP
rs991348084 297 dbSNP
rs1417258736 301 dbSNP
rs1050540503 305 dbSNP
rs1241872958 312 dbSNP
rs995868304 322 dbSNP
rs927976243 325 dbSNP
rs901473879 326 dbSNP
rs1265886077 328 dbSNP
rs1310379814 330 dbSNP
rs1341994204 333 dbSNP
rs757696423 335 dbSNP
rs1040146553 340 dbSNP
rs940417353 348 dbSNP
rs886307069 350 dbSNP
rs144315935 352 dbSNP
rs1351397847 357 dbSNP
rs1214624076 358 dbSNP
rs1262537394 360 dbSNP
rs538650455 361 dbSNP
rs916519440 363 dbSNP
rs79663100 364 dbSNP
rs989667361 368 dbSNP
rs1400338517 369 dbSNP
rs939364525 371 dbSNP
rs958481168 376 dbSNP
rs1184767580 384 dbSNP
rs1380289259 389 dbSNP
rs927930517 391 dbSNP
rs1438378775 395 dbSNP
rs1028058664 403 dbSNP
rs1345251078 415 dbSNP
rs1465257242 422 dbSNP
rs1165565170 432 dbSNP
rs1404099381 438 dbSNP
rs1453173542 441 dbSNP
rs752218525 445 dbSNP
rs978186647 447 dbSNP
rs997023672 452 dbSNP
rs1242198506 453 dbSNP
rs1309267179 454 dbSNP
rs186734767 457 dbSNP
rs1317549661 458 dbSNP
rs1232811672 476 dbSNP
rs764678375 487 dbSNP
rs1462816759 492 dbSNP
rs1243104718 505 dbSNP
rs1237923498 506 dbSNP
rs546759427 507 dbSNP
rs900812520 516 dbSNP
rs1179416420 525 dbSNP
rs1022916588 526 dbSNP
rs989647511 530 dbSNP
rs954333922 531 dbSNP
rs1004049948 533 dbSNP
rs1215429364 540 dbSNP
rs1351069599 541 dbSNP
rs759016266 542 dbSNP
rs1431056804 548 dbSNP
rs1246113388 558 dbSNP
rs998397790 566 dbSNP
rs572719767 567 dbSNP
rs1330484408 577 dbSNP
rs901546163 580 dbSNP
rs1018611840 582 dbSNP
rs1358061450 583 dbSNP
rs931155442 586 dbSNP
rs1383842112 596 dbSNP
rs528528416 597 dbSNP
rs1298609010 605 dbSNP
rs1004663829 606 dbSNP
rs776194842 608 dbSNP
rs886171069 610 dbSNP
rs927921964 624 dbSNP
rs1224337164 627 dbSNP
rs1049263583 648 dbSNP
rs982117467 657 dbSNP
rs1207253483 658 dbSNP
rs930506458 659 dbSNP
rs567441374 665 dbSNP
rs1488435947 673 dbSNP
rs1188988503 675 dbSNP
rs894939783 675 dbSNP
rs1288080229 682 dbSNP
rs1480572004 683 dbSNP
rs560189384 689 dbSNP
rs939269757 690 dbSNP
rs990167326 709 dbSNP
rs1349296357 737 dbSNP
rs548720278 756 dbSNP
rs1301427122 757 dbSNP
rs1028928144 759 dbSNP
rs530626602 761 dbSNP
rs1405819516 763 dbSNP
rs1384671043 764 dbSNP
rs978052415 767 dbSNP
rs1163370144 771 dbSNP
rs945488976 772 dbSNP
rs1216757922 781 dbSNP
rs915348731 782 dbSNP
rs975161418 787 dbSNP
rs989936517 790 dbSNP
rs35327755 791 dbSNP
rs1321693458 796 dbSNP
rs1219940402 812 dbSNP
rs1293355400 814 dbSNP
rs954238728 828 dbSNP
rs1192496190 829 dbSNP
rs183448674 836 dbSNP
rs1260666367 838 dbSNP
rs759331566 845 dbSNP
rs1476188243 856 dbSNP
rs191873843 873 dbSNP
rs1412773044 875 dbSNP
rs1487487849 877 dbSNP
rs1270643236 878 dbSNP
rs1165356035 879 dbSNP
rs1222738815 882 dbSNP
rs1490061275 883 dbSNP
rs1297650378 884 dbSNP
rs1425319748 884 dbSNP
rs397952366 884 dbSNP
rs374618512 888 dbSNP
rs1343691055 893 dbSNP
rs1028905301 897 dbSNP
rs75192338 898 dbSNP
rs78586314 899 dbSNP
rs1172886965 900 dbSNP
rs1244427937 900 dbSNP
rs1271158608 900 dbSNP
rs1433122973 900 dbSNP
rs1448421774 900 dbSNP
rs35786329 900 dbSNP
rs546766456 900 dbSNP
rs548307545 900 dbSNP
rs746988720 900 dbSNP
rs79906028 900 dbSNP
rs869032012 900 dbSNP
rs977033223 903 dbSNP
rs1236716768 905 dbSNP
rs1471652358 922 dbSNP
rs965606379 922 dbSNP
rs74015017 946 dbSNP
rs1308022177 950 dbSNP
rs886808412 959 dbSNP
rs1158172588 960 dbSNP
rs1026892328 962 dbSNP
rs1434202259 964 dbSNP
rs1004568935 973 dbSNP
rs886075214 984 dbSNP
rs1358960230 991 dbSNP
rs1285486425 1000 dbSNP
rs894287916 1013 dbSNP
rs1384238718 1024 dbSNP
rs1240028757 1025 dbSNP
rs139334502 1027 dbSNP
rs1365118880 1035 dbSNP
rs1002262192 1036 dbSNP
rs994957175 1038 dbSNP
rs1463545767 1040 dbSNP
rs1355655004 1041 dbSNP
rs1026296554 1049 dbSNP
rs541043389 1053 dbSNP
rs1170319111 1056 dbSNP
rs1205372634 1057 dbSNP
rs895019085 1065 dbSNP
rs1054877537 1067 dbSNP
rs1457276444 1076 dbSNP
rs1176654842 1091 dbSNP
rs151306294 1096 dbSNP
rs906444922 1099 dbSNP
rs1471167567 1101 dbSNP
rs773222914 1102 dbSNP
rs945344717 1106 dbSNP
rs1424806119 1113 dbSNP
rs1468404083 1117 dbSNP
rs1431882335 1118 dbSNP
rs1199786146 1121 dbSNP
rs913925838 1128 dbSNP
rs1446737971 1130 dbSNP
rs1327366257 1132 dbSNP
rs1054015288 1138 dbSNP
rs1442380204 1143 dbSNP
rs1273732433 1150 dbSNP
rs1321028961 1154 dbSNP
rs1224915509 1155 dbSNP
rs142439492 1162 dbSNP
rs1316997183 1171 dbSNP
rs62057170 1172 dbSNP
rs1480651006 1177 dbSNP
rs1252652411 1187 dbSNP
rs1438319783 1188 dbSNP
rs1182674525 1189 dbSNP
rs1250729307 1192 dbSNP
rs1246181977 1196 dbSNP
rs1196652642 1201 dbSNP
rs1201811416 1210 dbSNP
rs756268580 1210 dbSNP
rs1465382306 1214 dbSNP
rs764151956 1250 dbSNP
rs1399345604 1257 dbSNP
rs748046583 1258 dbSNP
rs774599898 1262 dbSNP
rs1222613643 1266 dbSNP
rs1343044763 1271 dbSNP
rs982525304 1276 dbSNP
rs1053913603 1277 dbSNP
rs575837330 1279 dbSNP
rs1330764154 1283 dbSNP
rs1283461735 1287 dbSNP
rs1339430134 1289 dbSNP
rs1225051659 1293 dbSNP
rs373748124 1302 dbSNP
rs1027085647 1308 dbSNP
rs560693597 1309 dbSNP
rs1209118207 1310 dbSNP
rs1291172654 1312 dbSNP
rs1489861159 1318 dbSNP
rs921469311 1322 dbSNP
rs571860480 1323 dbSNP
rs1269948071 1325 dbSNP
rs552918810 1329 dbSNP
rs1191540890 1330 dbSNP
rs965513888 1330 dbSNP
rs1476044092 1338 dbSNP
rs1163114294 1345 dbSNP
rs1034149625 1347 dbSNP
rs1002706857 1352 dbSNP
rs1426069486 1353 dbSNP
rs1303224061 1356 dbSNP
rs534698953 1358 dbSNP
rs1298161625 1359 dbSNP
rs1464518766 1368 dbSNP
rs982998233 1373 dbSNP
rs1046497930 1378 dbSNP
rs950416813 1390 dbSNP
rs892435595 1391 dbSNP
rs1224913809 1400 dbSNP
rs1292555089 1405 dbSNP
rs1485676144 1406 dbSNP
rs148792820 1414 dbSNP
rs1264300707 1417 dbSNP
rs1447880066 1420 dbSNP
rs574216891 1421 dbSNP
rs994631401 1429 dbSNP
rs921512507 1431 dbSNP
rs774194230 1438 dbSNP
rs117398185 1439 dbSNP
rs1033498166 1445 dbSNP
rs530614919 1449 dbSNP
rs944195779 1453 dbSNP
rs1419206120 1457 dbSNP
rs912755763 1464 dbSNP
rs1395302301 1471 dbSNP
rs982474304 1474 dbSNP
rs146161268 1477 dbSNP
rs1042285904 1485 dbSNP
rs1316341422 1486 dbSNP
rs1176160929 1487 dbSNP
rs188678203 1488 dbSNP
rs893839396 1493 dbSNP
rs1262772403 1506 dbSNP
rs749369204 1511 dbSNP
rs1351665790 1517 dbSNP
rs1203475014 1518 dbSNP
rs1263628750 1519 dbSNP
rs1202830368 1521 dbSNP
rs919568289 1526 dbSNP
rs932775203 1527 dbSNP
rs921367034 1529 dbSNP
rs1463069871 1533 dbSNP
rs1041122496 1535 dbSNP
rs780201876 1536 dbSNP
rs114741786 1550 dbSNP
rs1416733975 1555 dbSNP
rs958440313 1556 dbSNP
rs559390519 1560 dbSNP
rs547386466 1575 dbSNP
rs1468942881 1588 dbSNP
rs528910513 1592 dbSNP
rs1444585521 1594 dbSNP
rs1407972539 1601 dbSNP
rs1385654693 1608 dbSNP
rs1453288186 1609 dbSNP
rs953069805 1615 dbSNP
rs971194693 1616 dbSNP
rs920304270 1617 dbSNP
rs762808297 1633 dbSNP
rs1309196340 1635 dbSNP
rs1317796817 1636 dbSNP
rs1223081040 1649 dbSNP
rs1160000908 1650 dbSNP
rs183275054 1655 dbSNP
rs1009618991 1657 dbSNP
rs191811552 1674 dbSNP
rs1362798844 1678 dbSNP
rs1156328169 1679 dbSNP
rs1445878511 1684 dbSNP
rs142760817 1685 dbSNP
rs1243712544 1692 dbSNP
rs1182885062 1693 dbSNP
rs892547912 1697 dbSNP
rs1032466287 1698 dbSNP
Experimental Support 1 for Functional miRNA-Target Interaction
miRNA:Target ----
Validation Method
Conditions TZM-bl
Location of target site 3'UTR
Tools used in this research TargetScan , miRTarCLIP , Piranha
Original Description (Extracted from the article) ... PAR-CLIP data was present in GSM1462574. RNA binding protein: AGO2. Condition:TZM-bl ami BaL ...

- Whisnant AW; Bogerd HP; Flores O; Ho P; et al., 2013, mBio.

miRNA-target interactions (Provided by authors)
ID Duplex structure Position
1
miRNA  3' gauucugguucggaGGAAGGGa 5'
                        ||||||| 
Target 5' -------------aCCUUCCCc 3'
1 - 9
2
miRNA  3' gauucUGGUUCGGAGGAAGGGA----- 5'
               ||:  ||| :|||||:      
Target 5' ccccuACUCUGCC-UCUUCCUCCAUAC 3'
6 - 31
Article - Whisnant AW; Bogerd HP; Flores O; Ho P; et al.
- mBio, 2013
UNLABELLED: The question of how HIV-1 interfaces with cellular microRNA (miRNA) biogenesis and effector mechanisms has been highly controversial. Here, we first used deep sequencing of small RNAs present in two different infected cell lines (TZM-bl and C8166) and two types of primary human cells (CD4(+) peripheral blood mononuclear cells [PBMCs] and macrophages) to unequivocally demonstrate that HIV-1 does not encode any viral miRNAs. Perhaps surprisingly, we also observed that infection of T cells by HIV-1 has only a modest effect on the expression of cellular miRNAs at early times after infection. Comprehensive analysis of miRNA binding to the HIV-1 genome using the photoactivatable ribonucleoside-induced cross-linking and immunoprecipitation (PAR-CLIP) technique revealed several binding sites for cellular miRNAs, a subset of which were shown to be capable of mediating miRNA-mediated repression of gene expression. However, the main finding from this analysis is that HIV-1 transcripts are largely refractory to miRNA binding, most probably due to extensive viral RNA secondary structure. Together, these data demonstrate that HIV-1 neither encodes viral miRNAs nor strongly influences cellular miRNA expression, at least early after infection, and imply that HIV-1 transcripts have evolved to avoid inhibition by preexisting cellular miRNAs by adopting extensive RNA secondary structures that occlude most potential miRNA binding sites. IMPORTANCE: MicroRNAs (miRNAs) are a ubiquitous class of small regulatory RNAs that serve as posttranscriptional regulators of gene expression. Previous work has suggested that HIV-1 might subvert the function of the cellular miRNA machinery by expressing viral miRNAs or by dramatically altering the level of cellular miRNA expression. Using very sensitive approaches, we now demonstrate that neither of these ideas is in fact correct. Moreover, HIV-1 transcripts appear to largely avoid regulation by cellular miRNAs by adopting an extensive RNA secondary structure that occludes the ability of cellular miRNAs to interact with viral mRNAs. Together, these data suggest that HIV-1, rather than seeking to control miRNA function in infected cells, has instead evolved a mechanism to become largely invisible to cellular miRNA effector mechanisms.
LinkOut: [PMID: 23592263]
Experimental Support 2 for Functional miRNA-Target Interaction
miRNA:Target ----
Validation Method
Conditions HCT116
Location of target site 3'UTR
Tools used in this research TargetScan , miRTarCLIP , Piranha
Original Description (Extracted from the article) ... PAR-CLIP data was present in ERX177629. RNA binding protein: AGO2. Condition:KO_D_AGO_CLIP_4_7 ...

- Krell J; Stebbing J; Carissimi C; Dabrowska et al., 2016, Genome research.

Article - Krell J; Stebbing J; Carissimi C; Dabrowska et al.
- Genome research, 2016
DNA damage activates TP53-regulated surveillance mechanisms that are crucial in suppressing tumorigenesis. TP53 orchestrates these responses directly by transcriptionally modulating genes, including microRNAs (miRNAs), and by regulating miRNA biogenesis through interacting with the DROSHA complex. However, whether the association between miRNAs and AGO2 is regulated following DNA damage is not yet known. Here, we show that, following DNA damage, TP53 interacts with AGO2 to induce or reduce AGO2's association of a subset of miRNAs, including multiple let-7 family members. Furthermore, we show that specific mutations in TP53 decrease rather than increase the association of let-7 family miRNAs, reducing their activity without preventing TP53 from interacting with AGO2. This is consistent with the oncogenic properties of these mutants. Using AGO2 RIP-seq and PAR-CLIP-seq, we show that the DNA damage-induced increase in binding of let-7 family members to the RISC complex is functional. We unambiguously determine the global miRNA-mRNA interaction networks involved in the DNA damage response, validating them through the identification of miRNA-target chimeras formed by endogenous ligation reactions. We find that the target complementary region of the let-7 seed tends to have highly fixed positions and more variable ones. Additionally, we observe that miRNAs, whose cellular abundance or differential association with AGO2 is regulated by TP53, are involved in an intricate network of regulatory feedback and feedforward circuits. TP53-mediated regulation of AGO2-miRNA interaction represents a new mechanism of miRNA regulation in carcinogenesis.
LinkOut: [PMID: 26701625]
CLIP-seq Support 1 for dataset GSM1462574
Method / RBP PAR-CLIP / AGO2
Cell line / Condition TZM-bl / TZM-bl ami BaL
Location of target site ENST00000287461.3 | 3UTR | ACCUUCCCCUACUCUGCCUCUUCCUCCAUACUAG
Tools used in this analysis TargetScan, miRTarCLIP, and Piranha
Article / Accession Series PMID: 23592263 / GSE59944
CLIP-seq Viewer Link
MiRNA-Target Expression Profile
Dataset Pearson Correlation P-value for Pearson Correlation Spearman Correlation P-value for Spearman Correlation Samples Chart
MiRNA-Target Expression Profile (TCGA)
Tumor Pearson Correlation P-value for Pearson Correlation Spearman Correlation P-value for Spearman Correlation Samples Chart
215 hsa-miR-4747-5p Target Genes:
Functional analysis:
ID Target Description Validation methods
Strong evidence Less strong evidence
MIRT061689 BTG2 BTG anti-proliferation factor 2 2 2
MIRT062834 BCL7A BCL tumor suppressor 7A 2 2
MIRT079371 CCDC137 coiled-coil domain containing 137 2 2
MIRT081190 MIDN midnolin 2 4
MIRT081724 ZNF507 zinc finger protein 507 2 2
MIRT110565 ZMYND11 zinc finger MYND-type containing 11 2 2
MIRT133724 SKI SKI proto-oncogene 2 4
MIRT146689 MINK1 misshapen like kinase 1 2 2
MIRT150676 SLC27A1 solute carrier family 27 member 1 2 2
MIRT159196 NRBP1 nuclear receptor binding protein 1 2 2
MIRT180865 RPRD2 regulation of nuclear pre-mRNA domain containing 2 2 2
MIRT190659 PABPN1 poly(A) binding protein nuclear 1 2 2
MIRT196111 MPRIP myosin phosphatase Rho interacting protein 2 2
MIRT232390 SP1 Sp1 transcription factor 2 2
MIRT331070 EIF5AL1 eukaryotic translation initiation factor 5A-like 1 2 4
MIRT338632 SHMT2 serine hydroxymethyltransferase 2 2 2
MIRT407441 CTDSP1 CTD small phosphatase 1 2 2
MIRT444276 NKX6-1 NK6 homeobox 1 2 2
MIRT444834 PDE6D phosphodiesterase 6D 2 2
MIRT445452 EXT1 exostosin glycosyltransferase 1 2 2
MIRT445644 NPY4R neuropeptide Y receptor Y4 2 2
MIRT446157 RPL12 ribosomal protein L12 2 2
MIRT446608 HIP1 huntingtin interacting protein 1 2 2
MIRT447108 CLPX caseinolytic mitochondrial matrix peptidase chaperone subunit 2 2
MIRT449314 MRO maestro 2 2
MIRT450305 DRAXIN dorsal inhibitory axon guidance protein 2 2
MIRT451245 ZNF444 zinc finger protein 444 2 2
MIRT451714 OLR1 oxidized low density lipoprotein receptor 1 2 2
MIRT451908 ILK integrin linked kinase 2 2
MIRT452183 KIAA1456 KIAA1456 2 2
MIRT452610 REPIN1 replication initiator 1 2 2
MIRT453422 GLG1 golgi glycoprotein 1 2 2
MIRT454006 ALKBH5 alkB homolog 5, RNA demethylase 2 2
MIRT455072 ARHGAP39 Rho GTPase activating protein 39 2 2
MIRT455319 TTLL9 tubulin tyrosine ligase like 9 2 2
MIRT455357 KDM5C lysine demethylase 5C 2 2
MIRT455589 TAF12 TATA-box binding protein associated factor 12 2 2
MIRT455711 EIF4EBP2 eukaryotic translation initiation factor 4E binding protein 2 2 2
MIRT455860 TMEM254 transmembrane protein 254 2 2
MIRT455919 RAPGEF1 Rap guanine nucleotide exchange factor 1 2 2
MIRT455946 CYP4A22 cytochrome P450 family 4 subfamily A member 22 2 2
MIRT456935 LRP10 LDL receptor related protein 10 2 2
MIRT457223 AP3D1 adaptor related protein complex 3 delta 1 subunit 2 2
MIRT457431 NOL10 nucleolar protein 10 2 2
MIRT457470 SLC35F6 solute carrier family 35 member F6 2 2
MIRT457907 ZNF212 zinc finger protein 212 2 2
MIRT458046 TSEN54 tRNA splicing endonuclease subunit 54 2 2
MIRT458073 RNLS renalase, FAD dependent amine oxidase 2 2
MIRT458234 NXPH3 neurexophilin 3 2 2
MIRT458307 TNFAIP8L3 TNF alpha induced protein 8 like 3 2 2
MIRT458378 ITM2C integral membrane protein 2C 2 2
MIRT458967 ZNF436 zinc finger protein 436 2 2
MIRT459099 CYP4A11 cytochrome P450 family 4 subfamily A member 11 2 2
MIRT459446 TMEM37 transmembrane protein 37 2 2
MIRT459671 VPS37C VPS37C, ESCRT-I subunit 2 2
MIRT460727 ASXL3 additional sex combs like 3, transcriptional regulator 2 2
MIRT460744 SRP14 signal recognition particle 14 2 2
MIRT461531 C14orf1 ergosterol biosynthesis 28 homolog 2 2
MIRT461752 DDX11 DEAD/H-box helicase 11 2 2
MIRT461837 F2RL3 F2R like thrombin or trypsin receptor 3 2 2
MIRT462019 RIF1 replication timing regulatory factor 1 2 2
MIRT462631 PHF5A PHD finger protein 5A 2 2
MIRT462772 ZNF8 zinc finger protein 8 2 2
MIRT463032 ZNF689 zinc finger protein 689 2 2
MIRT463886 WNT7B Wnt family member 7B 2 2
MIRT463995 WDTC1 WD and tetratricopeptide repeats 1 2 2
MIRT464371 URM1 ubiquitin related modifier 1 2 2
MIRT465342 TPM3 tropomyosin 3 2 4
MIRT465515 PRICKLE4 prickle planar cell polarity protein 4 2 2
MIRT465602 TNRC6A trinucleotide repeat containing 6A 2 2
MIRT465697 TNPO2 transportin 2 2 10
MIRT466988 SSRP1 structure specific recognition protein 1 2 4
MIRT467630 SLC7A5 solute carrier family 7 member 5 2 2
MIRT468132 SH3PXD2A SH3 and PX domains 2A 2 2
MIRT468322 SF3B3 splicing factor 3b subunit 3 2 2
MIRT468502 SESN2 sestrin 2 2 2
MIRT468881 RREB1 ras responsive element binding protein 1 2 2
MIRT469322 RGP1 RGP1 homolog, RAB6A GEF complex partner 1 2 2
MIRT469562 RARA retinoic acid receptor alpha 2 2
MIRT469898 PTRF caveolae associated protein 1 2 2
MIRT470045 PTGFRN prostaglandin F2 receptor inhibitor 2 2
MIRT470068 PTGES2 prostaglandin E synthase 2 2 2
MIRT470238 PRRC2A proline rich coiled-coil 2A 2 2
MIRT470390 PPP1R16B protein phosphatase 1 regulatory subunit 16B 2 2
MIRT470500 PPP1R11 protein phosphatase 1 regulatory inhibitor subunit 11 2 2
MIRT470689 POLR2D RNA polymerase II subunit D 2 2
MIRT470704 POGK pogo transposable element derived with KRAB domain 2 2
MIRT471083 PIK3C2B phosphatidylinositol-4-phosphate 3-kinase catalytic subunit type 2 beta 2 2
MIRT472482 NACC2 NACC family member 2 2 2
MIRT473583 MAT2A methionine adenosyltransferase 2A 2 2
MIRT474554 KLHDC3 kelch domain containing 3 2 2
MIRT474651 KLF13 Kruppel like factor 13 2 2
MIRT474843 KHSRP KH-type splicing regulatory protein 2 2
MIRT474934 KCTD15 potassium channel tetramerization domain containing 15 2 2
MIRT475573 HNRNPC heterogeneous nuclear ribonucleoprotein C (C1/C2) 2 2
MIRT476045 GRSF1 G-rich RNA sequence binding factor 1 2 2
MIRT476080 GRB2 growth factor receptor bound protein 2 2 2
MIRT476440 GBA2 glucosylceramidase beta 2 2 2
MIRT476764 FOSL2 FOS like 2, AP-1 transcription factor subunit 2 2
MIRT478785 CRTC2 CREB regulated transcription coactivator 2 2 2
MIRT479287 CHAC1 ChaC glutathione specific gamma-glutamylcyclotransferase 1 2 2
MIRT479505 CDH6 cadherin 6 2 2
MIRT479732 CCND1 cyclin D1 2 6
MIRT480352 C5orf24 chromosome 5 open reading frame 24 2 2
MIRT480407 C19orf47 chromosome 19 open reading frame 47 2 2
MIRT480859 BHLHB9 basic helix-loop-helix family member b9 2 2
MIRT481445 ARRB2 arrestin beta 2 2 2
MIRT481732 APH1A aph-1 homolog A, gamma-secretase subunit 2 2
MIRT481824 AP2M1 adaptor related protein complex 2 mu 1 subunit 2 2
MIRT482566 ABHD2 abhydrolase domain containing 2 2 2
MIRT482607 ABHD14B abhydrolase domain containing 14B 2 2
MIRT483144 SYCE1L synaptonemal complex central element protein 1 like 2 2
MIRT483214 APOA1 apolipoprotein A1 2 6
MIRT483878 TGIF1 TGFB induced factor homeobox 1 2 2
MIRT483917 SPSB1 splA/ryanodine receptor domain and SOCS box containing 1 2 2
MIRT483939 LENG8 leukocyte receptor cluster member 8 2 4
MIRT484420 SNX19 sorting nexin 19 2 2
MIRT484489 SLC9A1 solute carrier family 9 member A1 2 2
MIRT484612 SIX3 SIX homeobox 3 2 6
MIRT484705 RNF11 ring finger protein 11 2 2
MIRT485107 SHISA6 shisa family member 6 2 2
MIRT485354 MYO1C myosin IC 2 4
MIRT485609 FOSL1 FOS like 1, AP-1 transcription factor subunit 2 4
MIRT487311 GLTSCR1 BRD4 interacting chromatin remodeling complex associated protein 2 2
MIRT487417 CACNB1 calcium voltage-gated channel auxiliary subunit beta 1 2 2
MIRT487695 CDK14 cyclin dependent kinase 14 2 2
MIRT487791 GPR20 G protein-coupled receptor 20 2 4
MIRT488042 PABPC1L2B poly(A) binding protein cytoplasmic 1 like 2B 2 2
MIRT488058 PABPC1L2A poly(A) binding protein cytoplasmic 1 like 2A 2 2
MIRT488237 DNLZ DNL-type zinc finger 2 4
MIRT488764 FXYD1 FXYD domain containing ion transport regulator 1 2 2
MIRT489401 TUBB2A tubulin beta 2A class IIa 2 2
MIRT489777 GRINA glutamate ionotropic receptor NMDA type subunit associated protein 1 2 2
MIRT490099 FN3K fructosamine 3 kinase 2 2
MIRT490290 ISL2 ISL LIM homeobox 2 2 2
MIRT490378 LHFPL3 LHFPL tetraspan subfamily member 3 2 2
MIRT491329 GFER growth factor, augmenter of liver regeneration 2 2
MIRT491435 MSX2 msh homeobox 2 2 2
MIRT491769 ZNF385A zinc finger protein 385A 2 2
MIRT491922 WNK2 WNK lysine deficient protein kinase 2 2 2
MIRT491983 UNK unkempt family zinc finger 2 2
MIRT492228 SLC48A1 solute carrier family 48 member 1 2 2
MIRT492404 SDK1 sidekick cell adhesion molecule 1 2 2
MIRT492767 PDGFB platelet derived growth factor subunit B 2 2
MIRT492966 NCS1 neuronal calcium sensor 1 2 2
MIRT493295 LLGL2 LLGL2, scribble cell polarity complex component 2 2
MIRT493650 HDLBP high density lipoprotein binding protein 2 2
MIRT493913 FAM127B retrotransposon Gag like 8A 2 4
MIRT495601 NKX2-5 NK2 homeobox 5 2 2
MIRT496875 AHCYL2 adenosylhomocysteinase like 2 2 2
MIRT498514 MYH14 myosin heavy chain 14 2 2
MIRT499178 RBPJL recombination signal binding protein for immunoglobulin kappa J region like 2 2
MIRT502143 KIF5B kinesin family member 5B 2 8
MIRT502692 CSNK1G1 casein kinase 1 gamma 1 2 4
MIRT508460 HOXB6 homeobox B6 2 4
MIRT510430 ZNF207 zinc finger protein 207 2 6
MIRT511837 GPATCH8 G-patch domain containing 8 2 4
MIRT512368 CPM carboxypeptidase M 2 2
MIRT512506 BTBD19 BTB domain containing 19 2 2
MIRT513065 ANKRD45 ankyrin repeat domain 45 2 2
MIRT513267 SCUBE1 signal peptide, CUB domain and EGF like domain containing 1 2 4
MIRT513575 EVX1 even-skipped homeobox 1 2 2
MIRT515051 EBNA1BP2 EBNA1 binding protein 2 2 2
MIRT515790 COL4A3BP collagen type IV alpha 3 binding protein 2 2
MIRT521657 PRKD3 protein kinase D3 2 2
MIRT522679 LUZP1 leucine zipper protein 1 2 6
MIRT528845 RAB32 RAB32, member RAS oncogene family 2 2
MIRT533569 TOR1AIP1 torsin 1A interacting protein 1 2 2
MIRT543738 DHCR7 7-dehydrocholesterol reductase 2 2
MIRT544295 TSPYL1 TSPY like 1 2 2
MIRT544857 MYH2 myosin heavy chain 2 2 4
MIRT557323 HIATL1 major facilitator superfamily domain containing 14B 2 4
MIRT560522 TMEM98 transmembrane protein 98 2 2
MIRT561565 SLC6A9 solute carrier family 6 member 9 2 2
MIRT562374 ERI2 ERI1 exoribonuclease family member 2 2 2
MIRT565780 SEMA6D semaphorin 6D 2 2
MIRT569548 UNC119B unc-119 lipid binding chaperone B 2 2
MIRT569944 PRRT2 proline rich transmembrane protein 2 2 2
MIRT570016 COL1A2 collagen type I alpha 2 chain 2 2
MIRT572163 CRK CRK proto-oncogene, adaptor protein 2 2
MIRT572322 HSPB6 heat shock protein family B (small) member 6 2 2
MIRT573495 IQSEC3 IQ motif and Sec7 domain 3 2 2
MIRT574139 MARVELD1 MARVEL domain containing 1 2 2
MIRT609449 CCDC149 coiled-coil domain containing 149 2 2
MIRT610619 ARHGAP18 Rho GTPase activating protein 18 2 2
MIRT623355 LZIC leucine zipper and CTNNBIP1 domain containing 2 2
MIRT629854 ACOX1 acyl-CoA oxidase 1 2 2
MIRT630516 CDC73 cell division cycle 73 2 2
MIRT632535 PSMB2 proteasome subunit beta 2 2 2
MIRT633975 SLC35E2 solute carrier family 35 member E2 2 2
MIRT636408 MTHFD2 methylenetetrahydrofolate dehydrogenase (NADP+ dependent) 2, methenyltetrahydrofolate cyclohydrolase 2 2
MIRT641722 LTBR lymphotoxin beta receptor 2 2
MIRT642661 RGS6 regulator of G protein signaling 6 2 2
MIRT649649 MAST3 microtubule associated serine/threonine kinase 3 2 2
MIRT650367 MOCS3 molybdenum cofactor synthesis 3 2 2
MIRT651355 ZBTB40 zinc finger and BTB domain containing 40 2 2
MIRT664840 HUS1 HUS1 checkpoint clamp component 2 2
MIRT667322 MYH9 myosin heavy chain 9 2 2
MIRT670680 SUGT1 SGT1 homolog, MIS12 kinetochore complex assembly cochaperone 2 2
MIRT674922 TRPM6 transient receptor potential cation channel subfamily M member 6 2 2
MIRT675919 CYP51A1 cytochrome P450 family 51 subfamily A member 1 2 2
MIRT676493 GJD3 gap junction protein delta 3 2 2
MIRT680162 ZDHHC20 zinc finger DHHC-type containing 20 2 2
MIRT688008 GSN gelsolin 2 2
MIRT688997 ATP6AP1 ATPase H+ transporting accessory protein 1 2 2
MIRT700337 RAB4A RAB4A, member RAS oncogene family 2 2
MIRT701344 NR4A3 nuclear receptor subfamily 4 group A member 3 2 2
MIRT703519 FKBP15 FK506 binding protein 15 2 2
MIRT703901 EPT1 selenoprotein I 2 2
MIRT705565 ARHGEF18 Rho/Rac guanine nucleotide exchange factor 18 2 2
MIRT709709 DNAJC11 DnaJ heat shock protein family (Hsp40) member C11 2 2
MIRT713108 TMBIM4 transmembrane BAX inhibitor motif containing 4 2 2
MIRT718426 ZNF85 zinc finger protein 85 2 2
MIRT719236 CYSLTR2 cysteinyl leukotriene receptor 2 2 2
MIRT719326 STAC SH3 and cysteine rich domain 2 2
miRNA-Drug Resistance Associations
miRNA Drug Name CID NSC FDA Effect/Pattern Detection Method Level Phenotype Condition
hsa-mir-4747 Paclitaxel 36314 NSC125973 approved resistant cell line (A2780)
hsa-miR-4747-5p Temozolomide 5394 NSC362856 approved sensitive cell line (U251)
hsa-miR-4747-5p Cisplatin 5460033 NSC119875 approved sensitive cell line (A549)
hsa-miR-4747-5p Gemcitabine 60750 NSC613327 approved sensitive cell line (PANC-1) (1500 ng/ml)

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