miRTarBase - #MIRT468835


—
pre-miRNA Information
pre-miRNA hsa-mir-4534   
Genomic Coordinates chr22: 37988794 - 37988853
Description Homo sapiens miR-4534 stem-loop
Comment None
RNA Secondary Structure

Mature miRNA Information
Mature miRNA hsa-miR-4534
Sequence 36| GGAUGGAGGAGGGGUCU |52
Evidence Experimental
Experiments Illumina
SNPs in miRNA
Mutant ID Mutant Position Mutant Source
rs890798116 2 dbSNP
rs1382774432 11 dbSNP
rs982883970 15 dbSNP
Putative Targets

miRNA Expression profile
Human miRNA Tissue Atlas
Circulating MicroRNA Expression Profiling
Gene Information
Gene Symbol RRM2   
Synonyms R2, RR2, RR2M
Description ribonucleotide reductase regulatory subunit M2
Transcript NM_001034   
Other Transcripts NM_001165931   
Expression
Putative miRNA Targets on RRM2
3'UTR of RRM2
(miRNA target sites are highlighted)		 
>RRM2|NM_001034|3'UTR
   1 ATGAACTGAAGATGTGCCCTTACTTGGCTGATTTTTTTTTTCCATCTCATAAGAAAAATCAGCTGAAGTGTTACCAACTA
  81 GCCACACCATGAATTGTCCGTAATGTTCATTAACAGCATCTTTAAAACTGTGTAGCTACCTCACAACCAGTCCTGTCTGT
 161 TTATAGTGCTGGTAGTATCACCTTTTGCCAGAAGGCCTGGCTGGCTGTGACTTACCATAGCAGTGACAATGGCAGTCTTG
 241 GCTTTAAAGTGAGGGGTGACCCTTTAGTGAGCTTAGCACAGCGGGATTAAACAGTCCTTTAACCAGCACAGCCAGTTAAA
 321 AGATGCAGCCTCACTGCTTCAACGCAGATTTTAATGTTTACTTAAATATAAACCTGGCACTTTACAAACAAATAAACATT
 401 GTTTGTACTCACAAGGCGATAATAGCTTGATTTATTTGGTTTCTACACCAAATACATTCTCCTGACCACTAATGGGAGCC
 481 AATTCACAATTCACTAAGTGACTAAAGTAAGTTAAACTTGTGTAGACTAAGCATGTAATTTTTAAGTTTTATTTTAATGA
 561 ATTAAAATATTTGTTAACCAACTTTAAAGTCAGTCCTGTGTATACCTAGATATTAGTCAGTTGGTGCCAGATAGAAGACA
 641 GGTTGTGTTTTTATCCTGTGGCTTGTGTAGTGTCCTGGGATTCTCTGCCCCCTCTGAGTAGAGTGTTGTGGGATAAAGGA
 721 ATCTCTCAGGGCAAGGAGCTTCTTAAGTTAAATCACTAGAAATTTAGGGGTGATCTGGGCCTTCATATGTGTGAGAAGCC
 801 GTTTCATTTTATTTCTCACTGTATTTTCCTCAACGTCTGGTTGATGAGAAAAAATTCTTGAAGAGTTTTCATATGTGGGA
 881 GCTAAGGTAGTATTGTAAAATTTCAAGTCATCCTTAAACAAAATGATCCACCTAAGATCTTGCCCCTGTTAAGTGGTGAA
 961 ATCAACTAGAGGTGGTTCCTACAAGTTGTTCATTCTAGTTTTGTTTGGTGTAAGTAGGTTGTGTGAGTTAATTCATTTAT
1041 ATTTACTATGTCTGTTAAATCAGAAATTTTTTATTATCTATGTTCTTCTAGATTTTACCTGTAGTTCATACTTCAGTCAC
1121 CCAGTGTCTTATTCTGGCATTGTCTAAATCTGAGCATTGTCTAGGGGGATCTTAAACTTTAGTAGGAAACCATGAGCTGT
1201 TAATACAGTTTCCATTCAAATATTAATTTCAGAATGAAACATAATTTTTTTTTTTTTTTTTGAGATGGAGTCTCGCTCTG
1281 TTGCCCAGGCTGGAGTGCAGTGGCGCGATTTTGGCTCACTGTAACCTCCATCTCCTGGGTTCAAGCAATTCTCCTGTCTC
1361 AGCCTCCCTAGTAGCTGGGACTGCAGGTATGTGCTACCACACCTGGCTAATTTTTGTATTTTTAGTAGAGATGGAGTTTC
1441 ACCATATTGGTCAGGCTGGTCTTGAACTCCTGACCTCAGGTGATCCACCCACCTCGGCCTCCCAAAGTGCTGGGATTGCA
1521 GGCGTGATAAACAAATATTCTTAATAGGGCTACTTTGAATTAATCTGCCTTTATGTTTGGGAGAAGAAAGCTGAGACATT
1601 GCATGAAAGATGATGAGAGATAAATGTTGATCTTTTGGCCCCATTTGTTAATTGTATTCAGTATTTGAACGTCGTCCTGT
1681 TTATTGTTAGTTTTCTTCATCATTTATTGTATAGACAATTTTTAAATCTCTGTAATATGATACATTTTCCTATCTTTTAA
1761 GTTATTGTTACCTAAAGTTAATCCAGATTATATGGTCCTTATATGTGTACAACATTAAAATGAAAGGCTTTGTCTTGCAT
1841 TGTGAGGTACAGGCGGAAGTTGGAATCAGGTTTTAGGATTCTGTCTCTCATTAGCTGAATAATGTGAGGATTAACTTCTG
1921 CCAGCTCAGACCATTTCCTAATCAGTTGAAAGGGAAACAAGTATTTCAGTCTCAAAATTGAATAATGCACAAGTCTTAAG
2001 TGATTAAAATAAAACTGTTCTTATGTCAGTTTCAAAAAAAAAAAAAAAAAA
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' ucuggggaGGAGGUAGg 5'
                  |||||||| 
Target 5' cactgtaaCCTCCATCt 3'
 1317 - 1333 145.00 -14.50
2 
miRNA  3' ucuGGGGAGGAGGUAGg 5'
             ::::|::|||||| 
Target 5' attTTTTTTTTCCATCt 3'
 31 - 47 134.00 -11.90
3 
miRNA  3' ucuggGGAGGAGGUAGg 5'
               ::|:||:|||| 
Target 5' gttagTTTTCTTCATCa 3'
 1686 - 1702 132.00 -11.80
DRVs in gene 3'UTRs
Mutant ID Mutant Position Mutant Source
COSN31485740 28 COSMIC
COSN1220591 42 COSMIC
COSN31613776 42 COSMIC
COSN30153780 49 COSMIC
COSN30518760 49 COSMIC
COSN31576965 51 COSMIC
COSN19312988 83 COSMIC
COSN31543880 101 COSMIC
COSN31583080 117 COSMIC
COSN28750194 135 COSMIC
COSN26677306 160 COSMIC
COSN19660334 181 COSMIC
COSN30120258 197 COSMIC
COSN31523393 299 COSMIC
COSN29192619 322 COSMIC
COSN6149472 348 COSMIC
COSN31488910 444 COSMIC
COSN29549608 451 COSMIC
COSN24013993 695 COSMIC
COSN30031157 786 COSMIC
COSN20096319 1262 COSMIC
COSN21407161 1359 COSMIC
COSN4909415 1519 COSMIC
COSN17376957 1675 COSMIC
SNPs in gene 3'UTRs
Mutant ID Mutant Position Mutant Source
rs756637379 2 dbSNP
rs778037879 11 dbSNP
rs749647333 16 dbSNP
rs771373014 17 dbSNP
rs376458388 22 dbSNP
rs371603045 32 dbSNP
rs764059345 32 dbSNP
rs78311808 32 dbSNP
rs756710024 33 dbSNP
rs79162203 33 dbSNP
rs1258460287 35 dbSNP
rs5030757 36 dbSNP
rs1247301601 38 dbSNP
rs1186886752 42 dbSNP
rs772288724 45 dbSNP
rs567302711 50 dbSNP
rs975301006 74 dbSNP
rs535862183 79 dbSNP
rs923485611 83 dbSNP
rs1469556842 86 dbSNP
rs1407301205 89 dbSNP
rs1179201192 94 dbSNP
rs186654277 100 dbSNP
rs151112936 101 dbSNP
rs1191897819 119 dbSNP
rs776799796 129 dbSNP
rs1263346898 131 dbSNP
rs1181385288 139 dbSNP
rs1460656066 140 dbSNP
rs538123832 147 dbSNP
rs978160437 156 dbSNP
rs1337429404 166 dbSNP
rs557947933 173 dbSNP
rs1250803716 178 dbSNP
rs577803252 191 dbSNP
rs1337026883 196 dbSNP
rs1358250641 198 dbSNP
rs1313101479 200 dbSNP
rs1445289424 202 dbSNP
rs1452269056 210 dbSNP
rs534347219 216 dbSNP
rs1383971126 226 dbSNP
rs1339160724 234 dbSNP
rs774957221 239 dbSNP
rs1390135279 244 dbSNP
rs1396354023 251 dbSNP
rs1291010685 256 dbSNP
rs1462000907 267 dbSNP
rs1363006245 270 dbSNP
rs5030759 273 dbSNP
rs1276845424 278 dbSNP
rs1325818883 279 dbSNP
rs1224170599 281 dbSNP
rs1277958451 283 dbSNP
rs1189412402 284 dbSNP
rs1310689264 286 dbSNP
rs936676506 288 dbSNP
rs191054082 306 dbSNP
rs914462632 307 dbSNP
rs1243639203 310 dbSNP
rs574906421 315 dbSNP
rs1341551311 324 dbSNP
rs139954791 344 dbSNP
rs79765591 354 dbSNP
rs1260893939 357 dbSNP
rs948688925 359 dbSNP
rs1317465871 367 dbSNP
rs1044599335 369 dbSNP
rs1335560801 384 dbSNP
rs1330065900 386 dbSNP
rs1393716129 388 dbSNP
rs1293078218 390 dbSNP
rs1423781056 394 dbSNP
rs534766369 398 dbSNP
rs1412401959 399 dbSNP
rs1047516544 409 dbSNP
rs545306582 410 dbSNP
rs1164662966 411 dbSNP
rs1468346086 417 dbSNP
rs1160832307 418 dbSNP
rs886230373 425 dbSNP
rs1005880515 429 dbSNP
rs144948625 434 dbSNP
rs1266824581 438 dbSNP
rs185874295 440 dbSNP
rs1490540373 442 dbSNP
rs996458906 444 dbSNP
rs1296935277 454 dbSNP
rs1347974724 456 dbSNP
rs1203621237 459 dbSNP
rs1406036418 460 dbSNP
rs1350404867 463 dbSNP
rs1280566860 467 dbSNP
rs1274351714 470 dbSNP
rs1241783878 480 dbSNP
rs1344219650 485 dbSNP
rs1342880009 490 dbSNP
rs1403746254 495 dbSNP
rs1030887637 502 dbSNP
rs547511857 503 dbSNP
rs1398648410 506 dbSNP
rs1383937331 512 dbSNP
rs1225756566 518 dbSNP
rs1473468129 519 dbSNP
rs1427053162 521 dbSNP
rs1198617243 529 dbSNP
rs867120429 532 dbSNP
rs1248599398 536 dbSNP
rs764106357 539 dbSNP
rs1285189270 544 dbSNP
rs1446688886 567 dbSNP
rs769909116 570 dbSNP
rs62129883 582 dbSNP
rs1321884767 594 dbSNP
rs1215667504 597 dbSNP
rs1224730997 606 dbSNP
rs1283557335 615 dbSNP
rs1345578234 617 dbSNP
rs1490823017 624 dbSNP
rs1031041610 632 dbSNP
rs10178011 646 dbSNP
rs201630221 666 dbSNP
rs1318588616 668 dbSNP
rs1458564138 677 dbSNP
rs549536921 678 dbSNP
rs1403643218 679 dbSNP
rs943264042 681 dbSNP
rs989423360 688 dbSNP
rs916604481 692 dbSNP
rs569278922 698 dbSNP
rs1475146749 699 dbSNP
rs1178627643 700 dbSNP
rs948615515 710 dbSNP
rs753857774 722 dbSNP
rs538183732 724 dbSNP
rs1367784495 725 dbSNP
rs868538774 726 dbSNP
rs928421140 733 dbSNP
rs938494630 739 dbSNP
rs551639029 756 dbSNP
rs886174658 766 dbSNP
rs1338195360 769 dbSNP
rs1270345626 773 dbSNP
rs941782920 776 dbSNP
rs114571498 779 dbSNP
rs1335896650 784 dbSNP
rs1444426961 801 dbSNP
rs900179009 802 dbSNP
rs1168269247 816 dbSNP
rs1409395441 818 dbSNP
rs534137052 830 dbSNP
rs1030584011 835 dbSNP
rs554292811 836 dbSNP
rs1384965126 840 dbSNP
rs192510398 847 dbSNP
rs1184546204 849 dbSNP
rs1484455676 849 dbSNP
rs536716140 855 dbSNP
rs556628299 860 dbSNP
rs1306809175 862 dbSNP
rs183195414 869 dbSNP
rs1281803697 874 dbSNP
rs34279704 877 dbSNP
rs999636218 890 dbSNP
rs5030760 894 dbSNP
rs766063643 916 dbSNP
rs958091335 920 dbSNP
rs545368074 927 dbSNP
rs1356877981 932 dbSNP
rs558883655 953 dbSNP
rs1289036676 954 dbSNP
rs1449420205 957 dbSNP
rs989538564 966 dbSNP
rs1206052309 970 dbSNP
rs1024025574 976 dbSNP
rs969421525 980 dbSNP
rs1438710470 992 dbSNP
rs1309978425 996 dbSNP
rs186091130 1002 dbSNP
rs1176327484 1004 dbSNP
rs1345067162 1011 dbSNP
rs1387548261 1020 dbSNP
rs1384789112 1022 dbSNP
rs1473323766 1024 dbSNP
rs1163227912 1025 dbSNP
rs1425857127 1050 dbSNP
rs1389243321 1053 dbSNP
rs190501818 1054 dbSNP
rs1470827314 1059 dbSNP
rs115318989 1074 dbSNP
rs928564013 1077 dbSNP
rs182776618 1081 dbSNP
rs578112183 1083 dbSNP
rs983263669 1085 dbSNP
rs1384781580 1089 dbSNP
rs907724615 1091 dbSNP
rs1350986799 1094 dbSNP
rs941729931 1098 dbSNP
rs1403118820 1099 dbSNP
rs1294335161 1104 dbSNP
rs775895379 1108 dbSNP
rs763139689 1115 dbSNP
rs1459694456 1117 dbSNP
rs749562845 1118 dbSNP
rs1283344483 1119 dbSNP
rs557816054 1121 dbSNP
rs1158890795 1126 dbSNP
rs537779131 1127 dbSNP
rs1401684000 1149 dbSNP
rs1414774756 1151 dbSNP
rs1354195765 1155 dbSNP
rs921556741 1169 dbSNP
rs1216202657 1170 dbSNP
rs1191388237 1183 dbSNP
rs1489278811 1190 dbSNP
rs931662559 1195 dbSNP
rs1051900862 1196 dbSNP
rs529769226 1198 dbSNP
rs200259620 1200 dbSNP
rs1269866533 1205 dbSNP
rs1196438457 1224 dbSNP
rs188323526 1229 dbSNP
rs1221682177 1230 dbSNP
rs562974254 1237 dbSNP
rs1302129685 1239 dbSNP
rs1388711150 1242 dbSNP
rs999752248 1243 dbSNP
rs1174906670 1245 dbSNP
rs1469794405 1245 dbSNP
rs34217469 1245 dbSNP
rs397732775 1245 dbSNP
rs1052524331 1246 dbSNP
rs1176102799 1250 dbSNP
rs1367025328 1258 dbSNP
rs76515542 1262 dbSNP
rs1368812454 1263 dbSNP
rs1458661866 1264 dbSNP
rs531969479 1271 dbSNP
rs1010908271 1273 dbSNP
rs1322786699 1275 dbSNP
rs1256549645 1276 dbSNP
rs571350098 1279 dbSNP
rs537185523 1284 dbSNP
rs557670968 1286 dbSNP
rs192657663 1289 dbSNP
rs1403223403 1291 dbSNP
rs182957125 1305 dbSNP
rs547688813 1306 dbSNP
rs187569312 1307 dbSNP
rs1335186484 1308 dbSNP
rs1003534411 1320 dbSNP
rs1403469692 1337 dbSNP
rs1486764240 1337 dbSNP
rs1338415452 1340 dbSNP
rs1305122528 1346 dbSNP
rs1467069531 1349 dbSNP
rs1370907241 1351 dbSNP
rs1167556947 1358 dbSNP
rs191269083 1364 dbSNP
rs557271849 1370 dbSNP
rs1035453135 1371 dbSNP
rs1316814582 1382 dbSNP
rs1460724229 1384 dbSNP
rs959919500 1389 dbSNP
rs1202115023 1390 dbSNP
rs1479697743 1391 dbSNP
rs983377685 1399 dbSNP
rs907675195 1407 dbSNP
rs963209913 1408 dbSNP
rs1313212042 1410 dbSNP
rs1345294125 1412 dbSNP
rs1138727 1417 dbSNP
rs1138728 1419 dbSNP
rs1341447993 1424 dbSNP
rs1390224534 1443 dbSNP
rs556689737 1445 dbSNP
rs1254596658 1447 dbSNP
rs570106471 1455 dbSNP
rs1449083925 1457 dbSNP
rs1429865865 1459 dbSNP
rs1195093344 1464 dbSNP
rs868811318 1468 dbSNP
rs1472306690 1478 dbSNP
rs539045567 1481 dbSNP
rs768854661 1490 dbSNP
rs1378217749 1491 dbSNP
rs1205895334 1494 dbSNP
rs1465735805 1496 dbSNP
rs1171036798 1499 dbSNP
rs1222111205 1519 dbSNP
rs1051414332 1520 dbSNP
rs774481698 1524 dbSNP
rs1237478567 1525 dbSNP
rs1293717473 1529 dbSNP
rs1401596289 1529 dbSNP
rs558946103 1542 dbSNP
rs1298778537 1545 dbSNP
rs879227886 1553 dbSNP
rs11545188 1557 dbSNP
rs935551266 1565 dbSNP
rs761886364 1600 dbSNP
rs184927325 1602 dbSNP
rs1339783024 1604 dbSNP
rs1398004225 1606 dbSNP
rs1451380670 1610 dbSNP
rs1411061886 1615 dbSNP
rs1182814201 1618 dbSNP
rs1284645672 1622 dbSNP
rs1184549612 1640 dbSNP
rs572272890 1641 dbSNP
rs772140952 1655 dbSNP
rs1331170638 1661 dbSNP
rs1232150210 1664 dbSNP
rs541289255 1671 dbSNP
rs1350428304 1672 dbSNP
rs1045671115 1674 dbSNP
rs1261362418 1675 dbSNP
rs905256462 1677 dbSNP
rs1217845952 1681 dbSNP
rs1138729 1684 dbSNP
rs1331272143 1684 dbSNP
rs1325126799 1697 dbSNP
rs1034987931 1710 dbSNP
rs374044024 1716 dbSNP
rs766135373 1717 dbSNP
rs951366002 1718 dbSNP
rs1004763662 1723 dbSNP
rs1487602398 1724 dbSNP
rs1014846857 1727 dbSNP
rs963323051 1728 dbSNP
rs1268231251 1729 dbSNP
rs1464727146 1737 dbSNP
rs761753577 1739 dbSNP
rs1211106202 1746 dbSNP
rs1322089756 1750 dbSNP
rs1432660907 1752 dbSNP
rs1278582773 1753 dbSNP
rs1197090565 1755 dbSNP
rs1218065965 1762 dbSNP
rs1345112949 1772 dbSNP
rs574555188 1779 dbSNP
rs973247082 1784 dbSNP
rs1365727737 1785 dbSNP
rs543162257 1786 dbSNP
rs145863886 1794 dbSNP
rs1321022057 1795 dbSNP
rs987635024 1799 dbSNP
rs1403754242 1804 dbSNP
rs767414325 1809 dbSNP
rs1415046382 1812 dbSNP
rs1417853770 1819 dbSNP
rs1427440420 1829 dbSNP
rs1166359293 1833 dbSNP
rs960282805 1843 dbSNP
rs1449148410 1849 dbSNP
rs934997491 1850 dbSNP
rs1295204849 1855 dbSNP
rs542863601 1856 dbSNP
rs1237340246 1863 dbSNP
rs530846614 1878 dbSNP
rs1280186489 1884 dbSNP
rs1385701584 1884 dbSNP
rs915482402 1886 dbSNP
rs1340971504 1889 dbSNP
rs1020623988 1891 dbSNP
rs1230269719 1896 dbSNP
rs946985020 1904 dbSNP
rs1448743452 1910 dbSNP
rs1298505362 1916 dbSNP
rs966394469 1930 dbSNP
rs532030581 1932 dbSNP
rs1371350459 1933 dbSNP
rs905370078 1934 dbSNP
rs1443154108 1935 dbSNP
rs13389058 1952 dbSNP
rs758777026 1958 dbSNP
rs979573058 1964 dbSNP
rs1182924764 1974 dbSNP
rs939416165 1980 dbSNP
rs1231704031 1984 dbSNP
rs1202345480 1991 dbSNP
rs1482450347 2005 dbSNP
rs1274841412 2012 dbSNP
rs925074527 2021 dbSNP
rs1351957475 2023 dbSNP
rs145536953 2024 dbSNP
rs1225446784 2025 dbSNP
rs1288926804 2028 dbSNP
Experimental Support 1 for Functional miRNA-Target Interaction
miRNA:Target ----
Validation Method
Conditions HEK293
Disease 6241.0
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 GSM714644. RNA binding protein: AGO2. Condition:completeT1 ...

- Kishore S; Jaskiewicz L; Burger L; Hausser et al., 2011, Nature methods.

miRNA-target interactions (Provided by authors)
ID Duplex structure Position
1 
miRNA  3' ucuggggaGGAGGuagg 5'
                  :||||    
Target 5' --------UCUCCuggg 3'
 		1 - 9
Article - Kishore S; Jaskiewicz L; Burger L; Hausser et al.
- Nature methods, 2011
Cross-linking and immunoprecipitation (CLIP) is increasingly used to map transcriptome-wide binding sites of RNA-binding proteins. We developed a method for CLIP data analysis, and applied it to compare CLIP with photoactivatable ribonucleoside-enhanced CLIP (PAR-CLIP) and to uncover how differences in cross-linking and ribonuclease digestion affect the identified sites. We found only small differences in accuracies of these methods in identifying binding sites of HuR, which binds low-complexity sequences, and Argonaute 2, which has a complex binding specificity. We found that cross-link-induced mutations led to single-nucleotide resolution for both PAR-CLIP and CLIP. Our results confirm the expectation from original CLIP publications that RNA-binding proteins do not protect their binding sites sufficiently under the denaturing conditions used during the CLIP procedure, and we show that extensive digestion with sequence-specific RNases strongly biases the recovered binding sites. This bias can be substantially reduced by milder nuclease digestion conditions.
LinkOut: [PMID: 21572407]
Experimental Support 2 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' ucuggggaGGAGGUAGg 5'
                  |||||||| 
Target 5' cacuguaaCCUCCAUCu 3'
 		3 - 19
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]
CLIP-seq Support 1 for dataset GSM4903833
Method / RBP HITS-CLIP / AGO
Cell line / Condition Dermal fibroblasts / CTL_TD_21_a
Location of target site NM_001165931 | 3UTR | AUCUCCUGGGUUCAAGCAAUUCUCCU
Tools used in this analysis TargetScan, miRTarCLIP, and Piranha
Accession Series GSE161239
CLIP-seq Viewer Link
CLIP-seq Support 2 for dataset GSM714644
Method / RBP PAR-CLIP / AGO2
Cell line / Condition HEK293 / completeT1, repA
Location of target site ENST00000360566.2 | 3UTR | UCUCCUGGGUUCAAGCAAU
Tools used in this analysis TargetScan, miRTarCLIP, and Piranha
Article / Accession Series PMID: 21572407 / GSE28865
CLIP-seq Viewer Link
CLIP-seq Support 3 for dataset GSM1462574
Method / RBP PAR-CLIP / AGO2
Cell line / Condition TZM-bl / TZM-bl ami BaL
Location of target site ENST00000360566.2 | 3UTR | CUCACUGUAACCUCCAUCUCCUGGGUUCAAG
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
141 hsa-miR-4534 Target Genes:
Functional analysis:
ID Target Description Validation methods
Strong evidence Less strong evidence
MIRT087131 CRKL CRK like proto-oncogene, adaptor protein 2 2
MIRT179641 CAPZA1 capping actin protein of muscle Z-line alpha subunit 1 2 2
MIRT243304 SLC25A36 solute carrier family 25 member 36 2 2
MIRT325574 HIATL1 major facilitator superfamily domain containing 14B 2 4
MIRT448776 GNA13 G protein subunit alpha 13 2 2
MIRT451456 HSD11B1L hydroxysteroid 11-beta dehydrogenase 1 like 2 2
MIRT452150 PPP2R1B protein phosphatase 2 scaffold subunit Abeta 2 2
MIRT454199 HLA-A major histocompatibility complex, class I, A 2 2
MIRT455984 ENPP5 ectonucleotide pyrophosphatase/phosphodiesterase 5 (putative) 2 2
MIRT456058 SLC25A28 solute carrier family 25 member 28 2 2
MIRT457082 XPNPEP3 X-prolyl aminopeptidase 3 2 2
MIRT457278 ALDH9A1 aldehyde dehydrogenase 9 family member A1 2 2
MIRT457361 POFUT2 protein O-fucosyltransferase 2 2 2
MIRT457396 CAMK2A calcium/calmodulin dependent protein kinase II alpha 2 2
MIRT458817 ZNF843 zinc finger protein 843 2 2
MIRT459697 VPS37C VPS37C, ESCRT-I subunit 2 2
MIRT460346 ARL14EP ADP ribosylation factor like GTPase 14 effector protein 2 2
MIRT462713 MAPK13 mitogen-activated protein kinase 13 2 2
MIRT464278 VASH1 vasohibin 1 2 2
MIRT465634 TNRC18P2 trinucleotide repeat containing 18 pseudogene 2 2 10
MIRT465772 TMOD3 tropomodulin 3 2 2
MIRT466414 TFDP1 transcription factor Dp-1 2 2
MIRT467122 SRGAP1 SLIT-ROBO Rho GTPase activating protein 1 2 8
MIRT467475 SMYD1 SET and MYND domain containing 1 2 4
MIRT468462 SET SET nuclear proto-oncogene 2 2
MIRT468618 SUMO1 small ubiquitin-like modifier 1 2 2
MIRT468835 RRM2 ribonucleotide reductase regulatory subunit M2 2 4
MIRT470890 PLXND1 plexin D1 2 2
MIRT473226 SMCR7L mitochondrial elongation factor 1 2 4
MIRT473858 MAP2K4 mitogen-activated protein kinase kinase 4 2 2
MIRT474975 KCND3 potassium voltage-gated channel subfamily D member 3 2 2
MIRT475858 H6PD hexose-6-phosphate dehydrogenase/glucose 1-dehydrogenase 2 2
MIRT478569 CTNND1 catenin delta 1 2 2
MIRT479347 CEP97 centrosomal protein 97 2 2
MIRT479910 CCDC117 coiled-coil domain containing 117 2 4
MIRT480122 CALR calreticulin 2 2
MIRT480892 BCL9L B-cell CLL/lymphoma 9 like 2 2
MIRT481149 AVL9 AVL9 cell migration associated 2 6
MIRT481527 ARL5B ADP ribosylation factor like GTPase 5B 2 10
MIRT481896 ANKRD40 ankyrin repeat domain 40 2 2
MIRT490138 FN3K fructosamine 3 kinase 2 4
MIRT490329 ANK1 ankyrin 1 2 4
MIRT491472 TMEM214 transmembrane protein 214 2 2
MIRT503552 TIGIT T-cell immunoreceptor with Ig and ITIM domains 2 4
MIRT504413 TUBA1B tubulin alpha 1b 2 4
MIRT508207 SLC35E1 solute carrier family 35 member E1 2 2
MIRT508333 SLC37A4 solute carrier family 37 member 4 2 6
MIRT516381 TRAF3IP2 TRAF3 interacting protein 2 2 4
MIRT518549 ABCA6 ATP binding cassette subfamily A member 6 2 2
MIRT522545 MED28 mediator complex subunit 28 2 6
MIRT522592 MAPK1IP1L mitogen-activated protein kinase 1 interacting protein 1 like 2 2
MIRT522923 KAT6A lysine acetyltransferase 6A 2 4
MIRT525937 C11orf74 chromosome 11 open reading frame 74 2 2
MIRT527021 PABPN1L poly(A) binding protein nuclear 1 like, cytoplasmic 2 2
MIRT530396 SULT1B1 sulfotransferase family 1B member 1 2 2
MIRT530660 TRIM56 tripartite motif containing 56 2 2
MIRT531625 TM4SF5 transmembrane 4 L six family member 5 2 4
MIRT532703 TCN2 transcobalamin 2 2 4
MIRT540173 MB21D1 Mab-21 domain containing 1 2 2
MIRT540756 UTP6 UTP6, small subunit processome component 2 2
MIRT541966 ZNF485 zinc finger protein 485 2 2
MIRT542738 RAF1 Raf-1 proto-oncogene, serine/threonine kinase 2 2
MIRT543090 KNSTRN kinetochore localized astrin/SPAG5 binding protein 2 2
MIRT550687 YARS tyrosyl-tRNA synthetase 2 2
MIRT553466 TNRC6A trinucleotide repeat containing 6A 2 2
MIRT559980 RELA RELA proto-oncogene, NF-kB subunit 2 2
MIRT561084 LLPH LLP homolog, long-term synaptic facilitation 2 2
MIRT561738 PLAGL2 PLAG1 like zinc finger 2 2 2
MIRT569872 KLK10 kallikrein related peptidase 10 2 2
MIRT570264 ARPC3 actin related protein 2/3 complex subunit 3 2 2
MIRT573431 ALDOA aldolase, fructose-bisphosphate A 2 2
MIRT573874 PRPS1L1 phosphoribosyl pyrophosphate synthetase 1-like 1 2 2
MIRT576905 Poteg POTE ankyrin domain family, member G 2 2
MIRT607934 ANG angiogenin 2 2
MIRT609472 RPL7L1 ribosomal protein L7 like 1 2 4
MIRT612179 EMC3 ER membrane protein complex subunit 3 2 2
MIRT613428 GALNT6 polypeptide N-acetylgalactosaminyltransferase 6 2 2
MIRT613746 GPR155 G protein-coupled receptor 155 2 2
MIRT615034 DIS3 DIS3 homolog, exosome endoribonuclease and 3'-5' exoribonuclease 2 2
MIRT615565 JPH2 junctophilin 2 2 2
MIRT615937 MAP1LC3B microtubule associated protein 1 light chain 3 beta 2 2
MIRT616643 LRAT lecithin retinol acyltransferase 2 4
MIRT630890 SLC25A33 solute carrier family 25 member 33 2 2
MIRT636542 FAM126B family with sequence similarity 126 member B 2 2
MIRT641392 NUBPL nucleotide binding protein like 2 2
MIRT641410 SCN2B sodium voltage-gated channel beta subunit 2 2 2
MIRT643184 HYPK huntingtin interacting protein K 2 2
MIRT652600 TIMM8A translocase of inner mitochondrial membrane 8A 2 2
MIRT653974 SEMA7A semaphorin 7A (John Milton Hagen blood group) 2 2
MIRT655692 NUDT3 nudix hydrolase 3 2 2
MIRT660734 ALG14 ALG14, UDP-N-acetylglucosaminyltransferase subunit 2 4
MIRT661604 C2orf15 chromosome 2 open reading frame 15 2 2
MIRT663284 ZNF675 zinc finger protein 675 2 2
MIRT666337 SKAP2 src kinase associated phosphoprotein 2 2 2
MIRT666636 RBMS2 RNA binding motif single stranded interacting protein 2 2 2
MIRT667125 OCIAD2 OCIA domain containing 2 2 2
MIRT670412 ELP2 elongator acetyltransferase complex subunit 2 2 2
MIRT671119 ZNF573 zinc finger protein 573 2 2
MIRT671152 ANKRD9 ankyrin repeat domain 9 2 2
MIRT671336 FAM71F2 family with sequence similarity 71 member F2 2 2
MIRT671867 ZNF429 zinc finger protein 429 2 2
MIRT671972 IKZF3 IKAROS family zinc finger 3 2 2
MIRT672062 KIAA0930 KIAA0930 2 2
MIRT672652 SLC25A16 solute carrier family 25 member 16 2 4
MIRT672671 GTF2H5 general transcription factor IIH subunit 5 2 2
MIRT672768 UBE2V2 ubiquitin conjugating enzyme E2 V2 2 2
MIRT672927 LRRC2 leucine rich repeat containing 2 2 2
MIRT673156 C1orf50 chromosome 1 open reading frame 50 2 2
MIRT673270 RUNDC1 RUN domain containing 1 2 2
MIRT673329 THAP1 THAP domain containing 1 2 2
MIRT673348 SLC35F6 solute carrier family 35 member F6 2 2
MIRT673664 ZNF440 zinc finger protein 440 2 2
MIRT673901 DCTN6 dynactin subunit 6 2 2
MIRT674399 MYCBP MYC binding protein 2 2
MIRT674523 PRR23A proline rich 23A 2 2
MIRT674831 ADAMTS4 ADAM metallopeptidase with thrombospondin type 1 motif 4 2 2
MIRT675064 FGD6 FYVE, RhoGEF and PH domain containing 6 2 2
MIRT675078 CCR6 C-C motif chemokine receptor 6 2 2
MIRT675123 FSD2 fibronectin type III and SPRY domain containing 2 2 2
MIRT679399 IL10RB interleukin 10 receptor subunit beta 2 2
MIRT686608 TMEM70 transmembrane protein 70 2 2
MIRT690371 ZSWIM7 zinc finger SWIM-type containing 7 2 2
MIRT694464 LRTOMT leucine rich transmembrane and O-methyltransferase domain containing 2 2
MIRT695706 OLA1 Obg like ATPase 1 2 2
MIRT696846 WDR13 WD repeat domain 13 2 2
MIRT700894 PER2 period circadian clock 2 2 2
MIRT701924 MLLT1 MLLT1, super elongation complex subunit 2 2
MIRT704918 CCDC36 coiled-coil domain containing 36 2 2
MIRT706211 ACOT9 acyl-CoA thioesterase 9 2 2
MIRT706546 GJD2 gap junction protein delta 2 2 2
MIRT706727 RFK riboflavin kinase 2 2
MIRT707366 ORAI2 ORAI calcium release-activated calcium modulator 2 2 2
MIRT707416 RRP7A ribosomal RNA processing 7 homolog A 2 2
MIRT710646 GLUL glutamate-ammonia ligase 2 2
MIRT712298 PGM2L1 phosphoglucomutase 2 like 1 2 2
MIRT713709 HIST3H2BB histone cluster 3 H2B family member b 2 2
MIRT713751 SLC9A8 solute carrier family 9 member A8 2 2
MIRT716423 VPS53 VPS53, GARP complex subunit 2 2
MIRT717169 UCHL3 ubiquitin C-terminal hydrolase L3 2 2
MIRT718877 PDIA3 protein disulfide isomerase family A member 3 2 2
MIRT720096 SPTLC3 serine palmitoyltransferase long chain base subunit 3 2 2
miRNA-Drug Associations
miRNA Small Melocule FDA CID Detection Method Condition PMID Year Expression Pattern of miRNA
miR-4 Dexamethasone approved 5743 Microarray primary rat thymocytes 20847043 2010 up-regulated
miRNA-Drug Resistance Associations
miRNA Drug Name CID NSC FDA Effect/Pattern Detection Method Level Phenotype Condition
hsa-miR-4534 Platinum 23939 sensitive High Ovarian Cancer tissue
hsa-miR-4534 Fluorouracil 3385 NSC19893 approved sensitive High Pancreatic Cancer cell line (PATU8988)
hsa-miR-4534 Dabrafenib 44462760 NSC764134 approved sensitive High Melanoma cell line (A375, IGR37, 501Mel)
hsa-miR-4534 Vemurafenib 42611257 NSC761431 approved sensitive High Melanoma cell line (A375, IGR37, 501Mel)
hsa-miR-4534 Fulvestrant 17756771 NSC719276 approved resistant High Breast Cancer cell line (MCF-7)
hsa-miR-4534 Tamoxifen 2733525 NSC180973 approved resistant High Breast Cancer cell line (MCF-7)
hsa-mir-4534 Androstenedione+Anastrozole sensitive cell line (MCF-7)
hsa-mir-4534 Cisplatin 5460033 NSC119875 approved resistant cell line (BxPC3)
hsa-miR-4534 Cisplatin 5460033 NSC119875 approved resistant cell line (CAL-27) (cytosolic RNA)
hsa-miR-4534 Doxorubicin 31703 NSC123127 approved sensitive cell line (BAS)
hsa-miR-4534 Osimertinib 71496458 NSC779217 approved sensitive cell line (H1975)
hsa-miR-4534 Paclitaxel 36314 NSC125973 approved resistant cell line (A2780)
hsa-miR-4534 Cisplatin 5460033 NSC119875 approved resistant cell line (A2780)
hsa-miR-4534 Platinum 23939 resistant tissue
hsa-miR-4534 Gemcitabine 60750 NSC613327 approved sensitive cell line (PANC-1) (1500 ng/ml)
hsa-miR-4534 Gemcitabine 60750 NSC613327 approved sensitive cell line (PANC-1) (100 ng/ml)
hsa-miR-4534 Cisplatin 5460033 NSC119875 approved resistant cell line (A549)

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