ID	Duplex structure	Position	Score	MFE
1	miRNA 3' ucGGUGUUAGUGGAAGACUAGa 5' | | || : | ||||:|| Target 5' aaCAAGAAGAGACATCTGGTCt 3'	1067 - 1088	132.00	-10.60
2	miRNA 3' ucgGUGUUAGUGG----AAGACUAGa 5' ||||:||||| ||:|| || Target 5' agaCACAGTCACCCAGTTTTTGTTCa 3'	477 - 502	129.00	-16.80
3	miRNA 3' ucGGUGUUAGUGGAAGACUAGa 5' || ::| |:|| |||||| Target 5' caCCCTGAACGCC-CCTGATCt 3'	1099 - 1119	127.00	-17.00

Mutant ID	Mutant Position	Mutant Source
COSN30474491	18	COSMIC
COSN31585029	47	COSMIC
COSN31559782	54	COSMIC
COSN17181620	55	COSMIC
COSN31563446	68	COSMIC
COSN30153501	78	COSMIC
COSN9828826	92	COSMIC
COSN20057663	129	COSMIC
COSN20070174	129	COSMIC
COSN20076159	130	COSMIC
COSN31536035	133	COSMIC
COSN30171341	166	COSMIC
COSN18719204	175	COSMIC
COSN31535844	260	COSMIC
COSN30538466	381	COSMIC
COSN2201225	484	COSMIC
COSN31533030	573	COSMIC
COSN9828827	611	COSMIC
COSN26638781	676	COSMIC
COSN30164328	760	COSMIC
COSN31530849	768	COSMIC
COSN26638782	831	COSMIC
COSN31538476	872	COSMIC
COSN31576039	937	COSMIC
COSN9922865	1287	COSMIC
COSN20091692	1294	COSMIC
COSN7959791	1338	COSMIC
COSN29354221	1443	COSMIC
COSN31529508	1514	COSMIC
COSN31608358	1627	COSMIC
COSN25781502	1629	COSMIC
COSN31602620	1789	COSMIC
COSN30173238	1800	COSMIC
COSN31521377	1820	COSMIC
COSN26564687	1864	COSMIC
rs11557288	1154	GWAS

Mutant ID	Mutant Position	Mutant Source
rs561516450	2	dbSNP
rs1283849481	6	dbSNP
rs548630950	16	dbSNP
rs774071452	17	dbSNP
rs1216153912	18	dbSNP
rs1258629731	23	dbSNP
rs374795819	24	dbSNP
rs772239945	26	dbSNP
rs773271929	28	dbSNP
rs367693210	31	dbSNP
rs1327929816	42	dbSNP
rs760861466	47	dbSNP
rs770904055	51	dbSNP
rs769964528	52	dbSNP
rs1173344439	53	dbSNP
rs1053093976	54	dbSNP
rs45578637	55	dbSNP
rs1169908885	61	dbSNP
rs1158654503	70	dbSNP
rs997274572	75	dbSNP
rs1428709544	76	dbSNP
rs1030108137	90	dbSNP
rs576793370	91	dbSNP
rs953259407	92	dbSNP
rs1301130893	94	dbSNP
rs1007885936	109	dbSNP
rs1270309842	110	dbSNP
rs1181509628	112	dbSNP
rs1002170139	118	dbSNP
rs906525506	118	dbSNP
rs540622556	129	dbSNP
rs963338518	130	dbSNP
rs1260707826	134	dbSNP
rs1224887380	137	dbSNP
rs1324163175	139	dbSNP
rs971744647	143	dbSNP
rs374338238	144	dbSNP
rs959765649	161	dbSNP
rs992603008	162	dbSNP
rs1337342323	171	dbSNP
rs916062442	174	dbSNP
rs1331076840	175	dbSNP
rs948949694	205	dbSNP
rs1447811428	209	dbSNP
rs1405716374	213	dbSNP
rs574192790	221	dbSNP
rs926229148	222	dbSNP
rs1226228016	225	dbSNP
rs1021112306	227	dbSNP
rs879009425	229	dbSNP
rs1468881771	242	dbSNP
rs1287267415	251	dbSNP
rs1234979281	258	dbSNP
rs1323779252	261	dbSNP
rs141846179	262	dbSNP
rs1460594118	263	dbSNP
rs902286388	266	dbSNP
rs934633031	270	dbSNP
rs768595292	274	dbSNP
rs1204988858	280	dbSNP
rs1323674619	282	dbSNP
rs997944283	282	dbSNP
rs563127571	283	dbSNP
rs1352502034	286	dbSNP
rs1279921116	288	dbSNP
rs1245050376	298	dbSNP
rs1335018202	299	dbSNP
rs1482892926	299	dbSNP
rs953723415	302	dbSNP
rs1359844625	316	dbSNP
rs530584628	317	dbSNP
rs1399474364	321	dbSNP
rs747147881	334	dbSNP
rs1159612835	335	dbSNP
rs1471457421	343	dbSNP
rs1382968838	346	dbSNP
rs1185084302	352	dbSNP
rs1241029648	355	dbSNP
rs1483262651	355	dbSNP
rs1016826243	356	dbSNP
rs1448650020	360	dbSNP
rs1430289434	361	dbSNP
rs1221420469	362	dbSNP
rs1357050141	364	dbSNP
rs962573896	364	dbSNP
rs10580617	366	dbSNP
rs114698645	366	dbSNP
rs1248463170	366	dbSNP
rs1347439761	366	dbSNP
rs138036238	366	dbSNP
rs1416015600	366	dbSNP
rs143325914	366	dbSNP
rs143579598	366	dbSNP
rs398006268	366	dbSNP
rs55725001	366	dbSNP
rs770671807	366	dbSNP
rs149250308	370	dbSNP
rs1424377646	371	dbSNP
rs1049837370	374	dbSNP
rs1174122388	376	dbSNP
rs1165024893	377	dbSNP
rs973001000	378	dbSNP
rs202117034	381	dbSNP
rs1184237016	383	dbSNP
rs1476132577	389	dbSNP
rs568624831	395	dbSNP
rs202032293	396	dbSNP
rs1007398527	413	dbSNP
rs1016553312	415	dbSNP
rs899097328	416	dbSNP
rs1322536841	421	dbSNP
rs564181656	426	dbSNP
rs1025968790	427	dbSNP
rs1364206459	428	dbSNP
rs1284294008	437	dbSNP
rs1055099704	448	dbSNP
rs959735060	456	dbSNP
rs1343952752	458	dbSNP
rs1305333301	460	dbSNP
rs992570673	460	dbSNP
rs1298561465	463	dbSNP
rs532549069	466	dbSNP
rs1353529025	471	dbSNP
rs114187848	472	dbSNP
rs970592593	474	dbSNP
rs1228093269	475	dbSNP
rs1276743769	483	dbSNP
rs1042990655	485	dbSNP
rs1459985976	499	dbSNP
rs1271031739	502	dbSNP
rs1191528955	514	dbSNP
rs1332833495	517	dbSNP
rs902674317	518	dbSNP
rs1232474996	528	dbSNP
rs1202721035	531	dbSNP
rs1320017563	540	dbSNP
rs566222433	541	dbSNP
rs536720503	542	dbSNP
rs1304103208	543	dbSNP
rs1387669879	544	dbSNP
rs1269313830	546	dbSNP
rs1373086322	547	dbSNP
rs1296037074	557	dbSNP
rs1006525000	561	dbSNP
rs1400667658	562	dbSNP
rs1016536378	572	dbSNP
rs1189629933	579	dbSNP
rs962641329	581	dbSNP
rs972667448	587	dbSNP
rs1025946879	589	dbSNP
rs1248165147	595	dbSNP
rs926169403	595	dbSNP
rs1429153641	596	dbSNP
rs971256411	600	dbSNP
rs981656860	601	dbSNP
rs1388907955	615	dbSNP
rs928044829	624	dbSNP
rs934899344	626	dbSNP
rs989045746	630	dbSNP
rs1258237221	632	dbSNP
rs1234623704	634	dbSNP
rs1316635356	635	dbSNP
rs548831803	638	dbSNP
rs1305306993	639	dbSNP
rs1242847262	645	dbSNP
rs752400745	646	dbSNP
rs1448189780	653	dbSNP
rs1304142956	655	dbSNP
rs878935072	670	dbSNP
rs1377150999	671	dbSNP
rs1367770053	673	dbSNP
rs922600751	675	dbSNP
rs934026632	676	dbSNP
rs938061976	680	dbSNP
rs1438205163	684	dbSNP
rs990845510	685	dbSNP
rs1362058749	689	dbSNP
rs1049763333	692	dbSNP
rs1366442124	693	dbSNP
rs915245046	698	dbSNP
rs1440125906	704	dbSNP
rs11760927	710	dbSNP
rs1382336950	711	dbSNP
rs1381109110	714	dbSNP
rs1183249377	722	dbSNP
rs1442800098	724	dbSNP
rs946994895	728	dbSNP
rs11557287	731	dbSNP
rs868103225	734	dbSNP
rs1259537972	753	dbSNP
rs1037530003	754	dbSNP
rs899018571	758	dbSNP
rs1292238922	760	dbSNP
rs537613397	761	dbSNP
rs35049738	762	dbSNP
rs1313854746	764	dbSNP
rs1323245056	765	dbSNP
rs1026270204	785	dbSNP
rs759832672	803	dbSNP
rs559205235	807	dbSNP
rs780042158	821	dbSNP
rs769999987	826	dbSNP
rs577424298	840	dbSNP
rs534662322	841	dbSNP
rs1006593028	843	dbSNP
rs1382664490	845	dbSNP
rs1246400692	849	dbSNP
rs552673839	850	dbSNP
rs1420033989	853	dbSNP
rs574228361	868	dbSNP
rs1190678459	871	dbSNP
rs541541682	872	dbSNP
rs1038034941	873	dbSNP
rs1246252509	893	dbSNP
rs1013931195	897	dbSNP
rs1428032883	897	dbSNP
rs563018892	898	dbSNP
rs969846246	901	dbSNP
rs753676350	902	dbSNP
rs1358011162	904	dbSNP
rs1365926271	904	dbSNP
rs1265713665	918	dbSNP
rs1033162520	925	dbSNP
rs956246467	926	dbSNP
rs575102817	935	dbSNP
rs1002736575	937	dbSNP
rs1406929331	938	dbSNP
rs1393112913	939	dbSNP
rs1164077393	944	dbSNP
rs1403997776	946	dbSNP
rs763483693	952	dbSNP
rs1034168201	955	dbSNP
rs191089608	957	dbSNP
rs764762927	958	dbSNP
rs564448361	960	dbSNP
rs146285024	962	dbSNP
rs1267551532	964	dbSNP
rs1194887380	965	dbSNP
rs1336804265	966	dbSNP
rs1321985800	978	dbSNP
rs1218775350	985	dbSNP
rs147977173	993	dbSNP
rs941438241	994	dbSNP
rs1434324362	995	dbSNP
rs1038901690	996	dbSNP
rs1331490451	1002	dbSNP
rs920419934	1006	dbSNP
rs1391040515	1009	dbSNP
rs924230737	1010	dbSNP
rs934224312	1011	dbSNP
rs929132447	1012	dbSNP
rs80150480	1014	dbSNP
rs575258120	1015	dbSNP
rs1378580749	1027	dbSNP
rs530078684	1035	dbSNP
rs1181628086	1037	dbSNP
rs1435706958	1038	dbSNP
rs1239675958	1047	dbSNP
rs1198694117	1049	dbSNP
rs1381226814	1053	dbSNP
rs1261118933	1055	dbSNP
rs895754249	1057	dbSNP
rs942836660	1058	dbSNP
rs1038087340	1059	dbSNP
rs1013899438	1070	dbSNP
rs1317811265	1070	dbSNP
rs898224718	1070	dbSNP
rs1333663619	1071	dbSNP
rs993860486	1071	dbSNP
rs1044053584	1080	dbSNP
rs879907826	1081	dbSNP
rs548721114	1095	dbSNP
rs907139790	1105	dbSNP
rs1403616941	1113	dbSNP
rs1003202350	1129	dbSNP
rs57720104	1131	dbSNP
rs958537639	1144	dbSNP
rs745374409	1147	dbSNP
rs1239763793	1149	dbSNP
rs11557288	1154	dbSNP
rs1211698509	1155	dbSNP
rs1033207402	1163	dbSNP
rs956171883	1164	dbSNP
rs1010360285	1165	dbSNP
rs141644782	1166	dbSNP
rs955611201	1174	dbSNP
rs571153290	1191	dbSNP
rs1307157175	1192	dbSNP
rs1196782245	1204	dbSNP
rs955683238	1217	dbSNP
rs987020591	1223	dbSNP
rs986142730	1231	dbSNP
rs80344027	1232	dbSNP
rs1336783450	1236	dbSNP
rs1360894688	1245	dbSNP
rs1038471118	1252	dbSNP
rs1423598876	1254	dbSNP
rs182642976	1255	dbSNP
rs919713159	1258	dbSNP
rs1009876053	1267	dbSNP
rs750008492	1274	dbSNP
rs1472863188	1276	dbSNP
rs1241407675	1277	dbSNP
rs1191446221	1278	dbSNP
rs1489110695	1282	dbSNP
rs755814438	1283	dbSNP
rs974151690	1284	dbSNP
rs537483999	1294	dbSNP
rs929101417	1295	dbSNP
rs1373735607	1297	dbSNP
rs768737866	1299	dbSNP
rs1230484216	1304	dbSNP
rs1270063540	1309	dbSNP
rs1398704576	1314	dbSNP
rs1055724747	1318	dbSNP
rs13241028	1322	dbSNP
rs556649681	1323	dbSNP
rs949978572	1327	dbSNP
rs1166514508	1328	dbSNP
rs1044745938	1335	dbSNP
rs530886427	1336	dbSNP
rs754907844	1347	dbSNP
rs1167997995	1348	dbSNP
rs1209948295	1352	dbSNP
rs1000009633	1353	dbSNP
rs1054091633	1357	dbSNP
rs1198378553	1365	dbSNP
rs778869257	1366	dbSNP
rs546026704	1370	dbSNP
rs1031050996	1371	dbSNP
rs1224060186	1382	dbSNP
rs955558308	1389	dbSNP
rs1257504468	1393	dbSNP
rs1180444796	1398	dbSNP
rs891563329	1402	dbSNP
rs1279432940	1405	dbSNP
rs557645333	1408	dbSNP
rs1223240329	1417	dbSNP
rs986739137	1424	dbSNP
rs1436743443	1440	dbSNP
rs1353618840	1443	dbSNP
rs1328659144	1457	dbSNP
rs1010330499	1458	dbSNP
rs1409362818	1459	dbSNP
rs1466767367	1467	dbSNP
rs1472060232	1469	dbSNP
rs1424198862	1470	dbSNP
rs1175640162	1471	dbSNP
rs1431172066	1474	dbSNP
rs542082787	1476	dbSNP
rs1029768801	1477	dbSNP
rs1403651128	1478	dbSNP
rs1237858091	1483	dbSNP
rs1196795575	1492	dbSNP
rs1412694890	1498	dbSNP
rs974232856	1502	dbSNP
rs1233176582	1505	dbSNP
rs867236745	1512	dbSNP
rs1311025788	1514	dbSNP
rs117268498	1515	dbSNP
rs1220224425	1520	dbSNP
rs929778051	1522	dbSNP
rs757287521	1529	dbSNP
rs1306667879	1534	dbSNP
rs540169569	1535	dbSNP
rs928366025	1545	dbSNP
rs938347962	1567	dbSNP
rs572268349	1568	dbSNP
rs1305948893	1572	dbSNP
rs1360885622	1576	dbSNP
rs962703786	1579	dbSNP
rs1224292608	1586	dbSNP
rs1379876884	1593	dbSNP
rs1418329098	1593	dbSNP
rs781354757	1597	dbSNP
rs111364957	1600	dbSNP
rs1238871913	1600	dbSNP
rs1042934650	1606	dbSNP
rs1342913165	1610	dbSNP
rs1482549614	1611	dbSNP
rs1258329416	1612	dbSNP
rs1211211579	1618	dbSNP
rs1025706912	1624	dbSNP
rs746016357	1627	dbSNP
rs998660461	1628	dbSNP
rs1031521617	1630	dbSNP
rs1203540427	1632	dbSNP
rs1311379340	1635	dbSNP
rs1393845432	1636	dbSNP
rs1381219371	1637	dbSNP
rs891180453	1655	dbSNP
rs992266743	1656	dbSNP
rs1358406414	1660	dbSNP
rs1157011544	1663	dbSNP
rs917084521	1666	dbSNP
rs1421739417	1677	dbSNP
rs1381203069	1680	dbSNP
rs1186890064	1682	dbSNP
rs1008210052	1686	dbSNP
rs1258809125	1691	dbSNP
rs1482533561	1693	dbSNP
rs751010509	1694	dbSNP
rs1488127829	1695	dbSNP
rs1284312610	1696	dbSNP
rs1219329176	1702	dbSNP
rs561935131	1708	dbSNP
rs139498398	1710	dbSNP
rs144317536	1711	dbSNP
rs1171447076	1727	dbSNP
rs935656062	1728	dbSNP
rs1299785523	1731	dbSNP
rs1431536137	1734	dbSNP
rs546301861	1737	dbSNP
rs951635705	1750	dbSNP
rs982949636	1755	dbSNP
rs1369643956	1758	dbSNP
rs928387843	1774	dbSNP
rs938400130	1777	dbSNP
rs1370272568	1779	dbSNP
rs1165649428	1782	dbSNP
rs1477771082	1783	dbSNP
rs1329542445	1797	dbSNP
rs1196264574	1798	dbSNP
rs1488840848	1800	dbSNP
rs1266172400	1805	dbSNP
rs1207716099	1826	dbSNP
rs1435899678	1828	dbSNP
rs1489137187	1836	dbSNP
rs991177414	1855	dbSNP
rs915578296	1863	dbSNP
rs1226767210	1868	dbSNP
rs1274379350	1869	dbSNP
rs1218960727	1872	dbSNP
rs947001798	1873	dbSNP
rs1043369128	1874	dbSNP
rs767446620	1875	dbSNP
rs750296322	1876	dbSNP
rs1211976967	1878	dbSNP
rs1326640528	1882	dbSNP
rs564106620	1883	dbSNP
rs1269068773	1884	dbSNP
rs1054061030	1887	dbSNP
rs891487944	1890	dbSNP

- Cell, 2010

RNA transcripts are subject to posttranscriptional gene regulation involving hundreds of RNA-binding proteins (RBPs) and microRNA-containing ribonucleoprotein complexes (miRNPs) expressed in a cell-type dependent fashion. We developed a cell-based crosslinking approach to determine at high resolution and transcriptome-wide the binding sites of cellular RBPs and miRNPs. The crosslinked sites are revealed by thymidine to cytidine transitions in the cDNAs prepared from immunopurified RNPs of 4-thiouridine-treated cells. We determined the binding sites and regulatory consequences for several intensely studied RBPs and miRNPs, including PUM2, QKI, IGF2BP1-3, AGO/EIF2C1-4 and TNRC6A-C. Our study revealed that these factors bind thousands of sites containing defined sequence motifs and have distinct preferences for exonic versus intronic or coding versus untranslated transcript regions. The precise mapping of binding sites across the transcriptome will be critical to the interpretation of the rapidly emerging data on genetic variation between individuals and how these variations contribute to complex genetic diseases.

- Genes & development, 2011

MicroRNAs are important regulators in many cellular processes, including stem cell self-renewal. Recent studies demonstrated their function as pluripotency factors with the capacity for somatic cell reprogramming. However, their role in human embryonic stem (ES) cells (hESCs) remains poorly understood, partially due to the lack of genome-wide strategies to identify their targets. Here, we performed comprehensive microRNA profiling in hESCs and in purified neural and mesenchymal derivatives. Using a combination of AGO cross-linking and microRNA perturbation experiments, together with computational prediction, we identified the targets of the miR-302/367 cluster, the most abundant microRNAs in hESCs. Functional studies identified novel roles of miR-302/367 in maintaining pluripotency and regulating hESC differentiation. We show that in addition to its role in TGF-beta signaling, miR-302/367 promotes bone morphogenetic protein (BMP) signaling by targeting BMP inhibitors TOB2, DAZAP2, and SLAIN1. This study broadens our understanding of microRNA function in hESCs and is a valuable resource for future studies in this area.

- 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.

- 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.