ID	Duplex structure	Position	Score	MFE
1	miRNA 3' gcggccCGAGGGGCCcc 5' || |||||| Target 5' attttaGC-CCCCGGca 3'	1145 - 1160	122.00	-14.20
2	miRNA 3' gcGGCCCGAGGGGCCCc 5' | | | |||| || Target 5' ctCAGAACACCCCAGGc 3'	1108 - 1124	111.00	-9.80
3	miRNA 3' gcggcccgaGGGGCCCc 5' || |||| Target 5' ccttctcgaCCACGGGa 3'	17 - 33	108.00	-13.80

Mutant ID	Mutant Position	Mutant Source
COSN30491191	5	COSMIC
COSN30491158	6	COSMIC
COSN20121944	15	COSMIC
COSN13570055	30	COSMIC
COSN30523562	46	COSMIC
COSN31566870	69	COSMIC
COSN30528507	84	COSMIC
COSN30726294	84	COSMIC
COSN1164084	90	COSMIC
COSN31533971	119	COSMIC
COSN31585560	153	COSMIC
COSN28852026	169	COSMIC
COSN31520561	199	COSMIC
COSN31481352	263	COSMIC
COSN26538290	264	COSMIC
COSN28250242	417	COSMIC
COSN28250492	439	COSMIC
COSN20677518	440	COSMIC
COSN28250243	451	COSMIC
COSN27091488	458	COSMIC
COSN28456979	458	COSMIC
COSN27453843	546	COSMIC
COSN26573035	561	COSMIC
COSN31530218	588	COSMIC
COSN31556391	645	COSMIC
COSN15568472	710	COSMIC
COSN31603339	711	COSMIC
COSN15568722	713	COSMIC
COSN31528852	751	COSMIC
COSN20995746	1197	COSMIC
COSN8139355	1410	COSMIC
COSN16412413	1547	COSMIC
COSN9609656	2386	COSMIC
COSN15904327	2722	COSMIC
COSN25278827	3510	COSMIC
COSN8821429	3580	COSMIC
COSN1164085	4637	COSMIC
COSN24961617	4819	COSMIC
rs9291	4908	GWAS

Mutant ID	Mutant Position	Mutant Source
rs372941821	7	dbSNP
rs1304671132	10	dbSNP
rs1053342194	14	dbSNP
rs189061079	18	dbSNP
rs367828506	22	dbSNP
rs180917436	24	dbSNP
rs547794853	25	dbSNP
rs770801130	29	dbSNP
rs776537905	30	dbSNP
rs1469650613	31	dbSNP
rs1342624144	33	dbSNP
rs1213307101	36	dbSNP
rs1241320125	42	dbSNP
rs975501706	43	dbSNP
rs745873295	50	dbSNP
rs1193610847	61	dbSNP
rs905889253	65	dbSNP
rs1271506138	67	dbSNP
rs1464381780	69	dbSNP
rs1209338859	83	dbSNP
rs920020295	88	dbSNP
rs1451313857	98	dbSNP
rs34152831	122	dbSNP
rs994910573	129	dbSNP
rs931298992	133	dbSNP
rs1249597973	143	dbSNP
rs564620331	148	dbSNP
rs1316180521	154	dbSNP
rs1442545199	156	dbSNP
rs1051870	157	dbSNP
rs112634633	157	dbSNP
rs1285031683	157	dbSNP
rs1433990378	157	dbSNP
rs533573122	158	dbSNP
rs1329153716	162	dbSNP
rs1392729579	173	dbSNP
rs1397503987	175	dbSNP
rs1368711187	182	dbSNP
rs908584827	187	dbSNP
rs1473604562	190	dbSNP
rs1005130615	197	dbSNP
rs940581147	199	dbSNP
rs1045706594	202	dbSNP
rs907015932	204	dbSNP
rs745476814	209	dbSNP
rs1387360330	211	dbSNP
rs1233777234	218	dbSNP
rs1184258157	225	dbSNP
rs1458219315	227	dbSNP
rs1323154292	228	dbSNP
rs1204383096	237	dbSNP
rs1055519913	241	dbSNP
rs184583794	244	dbSNP
rs1324243162	246	dbSNP
rs1404281441	247	dbSNP
rs1217357285	251	dbSNP
rs1344073753	257	dbSNP
rs965953553	258	dbSNP
rs1448546369	259	dbSNP
rs552290556	280	dbSNP
rs1452399267	281	dbSNP
rs1011199727	283	dbSNP
rs1342453976	285	dbSNP
rs1237237222	287	dbSNP
rs1332809655	293	dbSNP
rs569018486	294	dbSNP
rs1409195657	295	dbSNP
rs1279017550	309	dbSNP
rs1329944514	320	dbSNP
rs902889868	321	dbSNP
rs1184345068	325	dbSNP
rs1462728484	326	dbSNP
rs1269970384	328	dbSNP
rs1008417779	334	dbSNP
rs1019843377	335	dbSNP
rs964154540	339	dbSNP
rs1207942783	340	dbSNP
rs1441713538	341	dbSNP
rs537420872	342	dbSNP
rs1242039773	343	dbSNP
rs923695870	357	dbSNP
rs751597725	368	dbSNP
rs1246211370	411	dbSNP
rs548202226	411	dbSNP
rs1380718545	417	dbSNP
rs1256649008	418	dbSNP
rs1443785385	422	dbSNP
rs1179296808	433	dbSNP
rs997433340	441	dbSNP
rs1410509355	444	dbSNP
rs1472636217	446	dbSNP
rs934808006	459	dbSNP
rs1053716968	462	dbSNP
rs1427788148	467	dbSNP
rs758849334	472	dbSNP
rs189802069	489	dbSNP
rs952905697	490	dbSNP
rs1164483321	494	dbSNP
rs1173519498	503	dbSNP
rs982922055	515	dbSNP
rs755119446	518	dbSNP
rs533917619	519	dbSNP
rs534066844	524	dbSNP
rs1242595360	525	dbSNP
rs981331836	532	dbSNP
rs1227215764	534	dbSNP
rs1280678068	534	dbSNP
rs142338932	534	dbSNP
rs1487197156	534	dbSNP
rs541153352	534	dbSNP
rs57547470	534	dbSNP
rs796437804	534	dbSNP
rs950265613	534	dbSNP
rs928548853	535	dbSNP
rs1340301120	540	dbSNP
rs1389828686	545	dbSNP
rs1044690617	546	dbSNP
rs1328435726	546	dbSNP
rs1351133242	548	dbSNP
rs937156507	551	dbSNP
rs1281513524	564	dbSNP
rs1164217066	565	dbSNP
rs1321299844	566	dbSNP
rs1232531059	573	dbSNP
rs553655202	583	dbSNP
rs995278705	585	dbSNP
rs1195763992	588	dbSNP
rs1049108924	603	dbSNP
rs1346880474	615	dbSNP
rs1262283184	616	dbSNP
rs1193650196	619	dbSNP
rs886524985	620	dbSNP
rs1004695765	621	dbSNP
rs1407346756	624	dbSNP
rs551981689	629	dbSNP
rs752632596	640	dbSNP
rs947115892	647	dbSNP
rs965873781	657	dbSNP
rs781382083	663	dbSNP
rs902834465	664	dbSNP
rs1007862935	669	dbSNP
rs1388852816	670	dbSNP
rs1365813463	675	dbSNP
rs748421717	680	dbSNP
rs1293180328	681	dbSNP
rs1266231158	683	dbSNP
rs1028902380	687	dbSNP
rs967706675	688	dbSNP
rs1433099287	696	dbSNP
rs1464064384	698	dbSNP
rs1422797646	700	dbSNP
rs1176585696	701	dbSNP
rs1264954425	701	dbSNP
rs571482069	701	dbSNP
rs576589490	710	dbSNP
rs200210091	712	dbSNP
rs58262953	712	dbSNP
rs956676734	712	dbSNP
rs539290977	713	dbSNP
rs1317875935	724	dbSNP
rs1264272833	732	dbSNP
rs1177439715	734	dbSNP
rs1310838326	743	dbSNP
rs1379663638	749	dbSNP
rs991940189	753	dbSNP
rs1224603764	762	dbSNP
rs181348912	763	dbSNP
rs576511787	771	dbSNP
rs770684806	777	dbSNP
rs1303392001	800	dbSNP
rs1467462564	802	dbSNP
rs1375732569	803	dbSNP
rs1371377479	809	dbSNP
rs1431910247	829	dbSNP
rs1027559493	841	dbSNP
rs1301371029	849	dbSNP
rs778608183	855	dbSNP
rs930621069	860	dbSNP
rs1456945233	868	dbSNP
rs1367070711	874	dbSNP
rs1202708244	885	dbSNP
rs1482556651	886	dbSNP
rs541844584	890	dbSNP
rs1386089552	891	dbSNP
rs116126536	894	dbSNP
rs1332565860	898	dbSNP
rs1224997508	903	dbSNP
rs1273697427	904	dbSNP
rs1307377090	907	dbSNP
rs1342426419	908	dbSNP
rs886496574	913	dbSNP
rs1314866983	919	dbSNP
rs1397773199	933	dbSNP
rs572349944	934	dbSNP
rs376480416	939	dbSNP
rs537161562	945	dbSNP
rs1156487771	958	dbSNP
rs1438618909	960	dbSNP
rs928494343	964	dbSNP
rs1368601922	965	dbSNP
rs1189017858	966	dbSNP
rs958867731	972	dbSNP
rs1422627615	978	dbSNP
rs991453804	981	dbSNP
rs1217929559	982	dbSNP
rs1489494140	983	dbSNP
rs914375879	993	dbSNP
rs541702985	995	dbSNP
rs947261163	997	dbSNP
rs1041422323	1000	dbSNP
rs924374104	1002	dbSNP
rs1270118820	1010	dbSNP
rs564807937	1025	dbSNP
rs1427313957	1028	dbSNP
rs1242657682	1036	dbSNP
rs1028829030	1048	dbSNP
rs1040685501	1052	dbSNP
rs1311945606	1056	dbSNP
rs1400488189	1063	dbSNP
rs1342143388	1064	dbSNP
rs1296051275	1067	dbSNP
rs1418785518	1068	dbSNP
rs1390969005	1070	dbSNP
rs1164549539	1076	dbSNP
rs771913717	1083	dbSNP
rs145837831	1093	dbSNP
rs140658922	1094	dbSNP
rs1031073549	1095	dbSNP
rs1261551739	1101	dbSNP
rs553567023	1109	dbSNP
rs562554822	1112	dbSNP
rs1269708583	1114	dbSNP
rs1208233071	1119	dbSNP
rs1161921700	1125	dbSNP
rs991902888	1130	dbSNP
rs144198721	1144	dbSNP
rs531401224	1154	dbSNP
rs760256109	1157	dbSNP
rs1276118616	1158	dbSNP
rs1399146166	1164	dbSNP
rs1004396198	1167	dbSNP
rs1015651882	1171	dbSNP
rs906618171	1176	dbSNP
rs185771660	1187	dbSNP
rs776400600	1188	dbSNP
rs1378322915	1189	dbSNP
rs927543988	1190	dbSNP
rs568001738	1191	dbSNP
rs1422068726	1194	dbSNP
rs533564962	1197	dbSNP
rs985089147	1198	dbSNP
rs761597655	1200	dbSNP
rs765588514	1201	dbSNP
rs1296578182	1204	dbSNP
rs1197026932	1206	dbSNP
rs1021556929	1207	dbSNP
rs1365675848	1210	dbSNP
rs1451191497	1223	dbSNP
rs1238929011	1229	dbSNP
rs1200574087	1234	dbSNP
rs1230068871	1237	dbSNP
rs1256109445	1240	dbSNP
rs751074595	1240	dbSNP
rs796665802	1246	dbSNP
rs1345458728	1248	dbSNP
rs1276337037	1255	dbSNP
rs940730172	1263	dbSNP
rs1330141068	1265	dbSNP
rs369122781	1269	dbSNP
rs547281110	1270	dbSNP
rs1221628802	1276	dbSNP
rs943782889	1283	dbSNP
rs931794189	1284	dbSNP
rs1427709353	1306	dbSNP
rs1171169436	1325	dbSNP
rs1266744401	1325	dbSNP
rs976500312	1329	dbSNP
rs1381130971	1331	dbSNP
rs750767036	1332	dbSNP
rs1437942025	1335	dbSNP
rs920912030	1344	dbSNP
rs1203751143	1348	dbSNP
rs932353033	1355	dbSNP
rs138466459	1356	dbSNP
rs1198480510	1357	dbSNP
rs1181938513	1360	dbSNP
rs143029462	1364	dbSNP
rs1413374497	1370	dbSNP
rs940130900	1374	dbSNP
rs1309556226	1375	dbSNP
rs1424666691	1381	dbSNP
rs1241811869	1387	dbSNP
rs1166993636	1393	dbSNP
rs1374021224	1396	dbSNP
rs1278384890	1398	dbSNP
rs1037197544	1400	dbSNP
rs1013263721	1401	dbSNP
rs143244678	1404	dbSNP
rs1414281930	1406	dbSNP
rs866761503	1414	dbSNP
rs190626232	1422	dbSNP
rs1033791663	1428	dbSNP
rs980236754	1439	dbSNP
rs1319811216	1441	dbSNP
rs1182518046	1446	dbSNP
rs1473109485	1449	dbSNP
rs1239105526	1452	dbSNP
rs1185263287	1457	dbSNP
rs148287918	1458	dbSNP
rs1286381768	1470	dbSNP
rs1218356362	1472	dbSNP
rs1010917098	1493	dbSNP
rs555586651	1494	dbSNP
rs572394068	1497	dbSNP
rs968606105	1499	dbSNP
rs961980934	1501	dbSNP
rs977342467	1502	dbSNP
rs976073371	1509	dbSNP
rs1300911185	1510	dbSNP
rs541481821	1527	dbSNP
rs755031708	1528	dbSNP
rs558467567	1529	dbSNP
rs578258466	1538	dbSNP
rs181767912	1542	dbSNP
rs1228603447	1550	dbSNP
rs1418176412	1556	dbSNP
rs780939219	1570	dbSNP
rs1165632129	1573	dbSNP
rs1407172471	1578	dbSNP
rs1411664676	1587	dbSNP
rs1161391522	1588	dbSNP
rs1474806611	1589	dbSNP
rs1263705711	1591	dbSNP
rs1195568231	1593	dbSNP
rs932057465	1599	dbSNP
rs965208578	1609	dbSNP
rs141469146	1621	dbSNP
rs1228248167	1623	dbSNP
rs1323004213	1625	dbSNP
rs1287058364	1631	dbSNP
rs921035570	1637	dbSNP
rs1280538121	1639	dbSNP
rs1398522011	1653	dbSNP
rs113808557	1654	dbSNP
rs1294369906	1655	dbSNP
rs936550022	1658	dbSNP
rs1325285193	1670	dbSNP
rs1052746144	1674	dbSNP
rs35681390	1687	dbSNP
rs756308700	1689	dbSNP
rs940245207	1690	dbSNP
rs778708668	1692	dbSNP
rs1418447238	1712	dbSNP
rs1191426628	1715	dbSNP
rs1013234001	1716	dbSNP
rs112692624	1717	dbSNP
rs1212490631	1721	dbSNP
rs369740678	1723	dbSNP
rs1458645717	1727	dbSNP
rs1260571841	1732	dbSNP
rs1237333655	1734	dbSNP
rs1046108849	1741	dbSNP
rs1307286004	1742	dbSNP
rs1183828409	1748	dbSNP
rs1221211323	1749	dbSNP
rs868677902	1752	dbSNP
rs928097209	1761	dbSNP
rs143614395	1762	dbSNP
rs553082698	1763	dbSNP
rs1026769225	1764	dbSNP
rs1055586249	1772	dbSNP
rs952277368	1773	dbSNP
rs527277426	1775	dbSNP
rs895237080	1776	dbSNP
rs1158266233	1779	dbSNP
rs1011449052	1791	dbSNP
rs1412587778	1802	dbSNP
rs1006393216	1813	dbSNP
rs547019250	1835	dbSNP
rs1458787538	1836	dbSNP
rs902551849	1842	dbSNP
rs796856049	1847	dbSNP
rs1358425672	1848	dbSNP
rs367886972	1854	dbSNP
rs1448231939	1859	dbSNP
rs147227195	1865	dbSNP
rs1192564662	1866	dbSNP
rs976335008	1867	dbSNP
rs112354737	1871	dbSNP
rs1480584541	1877	dbSNP
rs1212645328	1878	dbSNP
rs1310713957	1880	dbSNP
rs1302990639	1885	dbSNP
rs1241062505	1892	dbSNP
rs569788182	1893	dbSNP
rs953421169	1903	dbSNP
rs965156235	1904	dbSNP
rs140635852	1906	dbSNP
rs925395867	1913	dbSNP
rs1331801651	1920	dbSNP
rs1303265727	1925	dbSNP
rs746990203	1928	dbSNP
rs1028451676	1939	dbSNP
rs1373347115	1943	dbSNP
rs1172628925	1950	dbSNP
rs953818143	1954	dbSNP
rs984309906	1958	dbSNP
rs913790061	1960	dbSNP
rs909533360	1961	dbSNP
rs1212458581	1962	dbSNP
rs1249913766	1967	dbSNP
rs560780157	1967	dbSNP
rs1482877750	1968	dbSNP
rs1046369656	1972	dbSNP
rs1182946242	1973	dbSNP
rs1254159541	1975	dbSNP
rs904856606	1978	dbSNP
rs748284473	1979	dbSNP
rs1284027273	1983	dbSNP
rs1238398714	1997	dbSNP
rs1341093481	2017	dbSNP
rs1189418714	2019	dbSNP
rs961053556	2020	dbSNP
rs1424128049	2022	dbSNP
rs1353341261	2023	dbSNP
rs566067601	2027	dbSNP
rs768249591	2028	dbSNP
rs888222717	2037	dbSNP
rs972954333	2037	dbSNP
rs964843176	2038	dbSNP
rs1428752155	2043	dbSNP
rs1368474384	2052	dbSNP
rs928211444	2057	dbSNP
rs1167545369	2064	dbSNP
rs776311735	2064	dbSNP
rs1055297462	2067	dbSNP
rs1015035215	2068	dbSNP
rs1489424673	2072	dbSNP
rs144483706	2075	dbSNP
rs1351810453	2076	dbSNP
rs558149824	2081	dbSNP
rs1357143808	2084	dbSNP
rs1267236878	2085	dbSNP
rs962210973	2091	dbSNP
rs769725457	2097	dbSNP
rs1218990678	2107	dbSNP
rs144448105	2108	dbSNP
rs1274808481	2109	dbSNP
rs557386453	2111	dbSNP
rs187504779	2112	dbSNP
rs1390902326	2115	dbSNP
rs902500919	2120	dbSNP
rs574169726	2121	dbSNP
rs1032815211	2124	dbSNP
rs1479026670	2132	dbSNP
rs1272983338	2139	dbSNP
rs1341714454	2145	dbSNP
rs958160973	2147	dbSNP
rs1452390479	2151	dbSNP
rs1052932169	2159	dbSNP
rs901097579	2162	dbSNP
rs1276795895	2169	dbSNP
rs1272494388	2176	dbSNP
rs998548425	2183	dbSNP
rs1219120807	2186	dbSNP
rs1319756552	2188	dbSNP
rs1226323383	2198	dbSNP
rs1268186351	2198	dbSNP
rs1331294871	2205	dbSNP
rs1302838623	2208	dbSNP
rs1219238581	2214	dbSNP
rs1438112240	2216	dbSNP
rs1028147124	2224	dbSNP
rs190631072	2228	dbSNP
rs376868103	2229	dbSNP
rs1192679096	2231	dbSNP
rs773484960	2242	dbSNP
rs1394854277	2247	dbSNP
rs1167691416	2251	dbSNP
rs1388163855	2254	dbSNP
rs1478500554	2257	dbSNP
rs981991463	2268	dbSNP
rs1005283490	2270	dbSNP
rs926530195	2271	dbSNP
rs1371824943	2280	dbSNP
rs1199258843	2283	dbSNP
rs747745690	2288	dbSNP
rs1322356955	2293	dbSNP
rs1194991832	2294	dbSNP
rs961001697	2296	dbSNP
rs1048072882	2306	dbSNP
rs972395906	2317	dbSNP
rs1439298403	2320	dbSNP
rs1458192009	2322	dbSNP
rs148401591	2328	dbSNP
rs1449734611	2342	dbSNP
rs1334471273	2346	dbSNP
rs763101005	2349	dbSNP
rs1364944911	2351	dbSNP
rs1415424946	2354	dbSNP
rs939769265	2355	dbSNP
rs960980659	2359	dbSNP
rs1172011343	2362	dbSNP
rs1036783186	2379	dbSNP
rs1180554044	2382	dbSNP
rs1471147973	2388	dbSNP
rs1231131899	2390	dbSNP
rs991507936	2401	dbSNP
rs1030499284	2410	dbSNP
rs1346692849	2410	dbSNP
rs897993736	2410	dbSNP
rs997645222	2410	dbSNP
rs889391511	2412	dbSNP
rs1007943253	2414	dbSNP
rs1032330366	2417	dbSNP
rs916739042	2417	dbSNP
rs142584290	2419	dbSNP
rs766570594	2424	dbSNP
rs769336298	2425	dbSNP
rs1311438672	2432	dbSNP
rs1414437249	2433	dbSNP
rs1361387252	2434	dbSNP
rs775326781	2439	dbSNP
rs1399062250	2448	dbSNP
rs1407266373	2450	dbSNP
rs924037022	2451	dbSNP
rs935292737	2455	dbSNP
rs1040348098	2460	dbSNP
rs1259429158	2465	dbSNP
rs1215499796	2468	dbSNP
rs772985729	2476	dbSNP
rs1444783661	2481	dbSNP
rs981960491	2481	dbSNP
rs1282870798	2482	dbSNP
rs937931365	2484	dbSNP
rs1337547602	2486	dbSNP
rs1291879315	2500	dbSNP
rs933911303	2501	dbSNP
rs1341480831	2510	dbSNP
rs1290862144	2513	dbSNP
rs1428828142	2514	dbSNP
rs1344749369	2517	dbSNP
rs984470242	2518	dbSNP
rs1324274486	2521	dbSNP
rs1231312404	2522	dbSNP
rs1405918705	2535	dbSNP
rs763215827	2566	dbSNP
rs540744455	2568	dbSNP
rs909549316	2570	dbSNP
rs182817725	2583	dbSNP
rs1423987194	2585	dbSNP
rs187784344	2588	dbSNP
rs1474214055	2594	dbSNP
rs889603886	2610	dbSNP
rs1162120848	2612	dbSNP
rs1036703371	2613	dbSNP
rs1271862772	2614	dbSNP
rs1407523720	2619	dbSNP
rs150952803	2624	dbSNP
rs933465012	2625	dbSNP
rs889310890	2627	dbSNP
rs796511676	2628	dbSNP
rs1436310593	2629	dbSNP
rs1323026870	2635	dbSNP
rs1443222953	2648	dbSNP
rs540946090	2653	dbSNP
rs1016655462	2654	dbSNP
rs1460803064	2660	dbSNP
rs564294776	2665	dbSNP
rs993953291	2669	dbSNP
rs1034671578	2675	dbSNP
rs796584398	2676	dbSNP
rs1009573333	2687	dbSNP
rs1021027864	2690	dbSNP
rs191346682	2705	dbSNP
rs960678792	2712	dbSNP
rs1455197825	2713	dbSNP
rs1250536987	2714	dbSNP
rs970816253	2715	dbSNP
rs991065989	2721	dbSNP
rs529061658	2722	dbSNP
rs968211548	2725	dbSNP
rs959508730	2731	dbSNP
rs984049307	2734	dbSNP
rs1236686729	2745	dbSNP
rs1368887182	2746	dbSNP
rs979571115	2757	dbSNP
rs909795669	2758	dbSNP
rs924149739	2769	dbSNP
rs1373939836	2770	dbSNP
rs1266188170	2772	dbSNP
rs1299765981	2775	dbSNP
rs1460305397	2789	dbSNP
rs935408647	2791	dbSNP
rs1328455325	2793	dbSNP
rs961034756	2795	dbSNP
rs760430899	2802	dbSNP
rs1263663690	2805	dbSNP
rs922329002	2826	dbSNP
rs764142059	2828	dbSNP
rs933730664	2834	dbSNP
rs1253308311	2839	dbSNP
rs1175948457	2850	dbSNP
rs1480512112	2851	dbSNP
rs1440321421	2855	dbSNP
rs976163376	2857	dbSNP
rs1049492422	2860	dbSNP
rs548939085	2862	dbSNP
rs1237488782	2870	dbSNP
rs1279755902	2875	dbSNP
rs923278960	2878	dbSNP
rs1240993150	2880	dbSNP
rs767541226	2888	dbSNP
rs1318771508	2890	dbSNP
rs1309065624	2891	dbSNP
rs1475922739	2895	dbSNP
rs1157529577	2902	dbSNP
rs1313260901	2905	dbSNP
rs931993285	2911	dbSNP
rs373645064	2940	dbSNP
rs1416292035	2948	dbSNP
rs1411846941	2951	dbSNP
rs1049636710	2952	dbSNP
rs1453889408	2969	dbSNP
rs1364953756	2970	dbSNP
rs1157571578	2975	dbSNP
rs1418990918	2986	dbSNP
rs889708055	3002	dbSNP
rs1160653189	3003	dbSNP
rs1054007439	3004	dbSNP
rs1009542066	3007	dbSNP
rs894067489	3007	dbSNP
rs1042397220	3017	dbSNP
rs1400590278	3017	dbSNP
rs1395600514	3018	dbSNP
rs1335136822	3019	dbSNP
rs1342293163	3021	dbSNP
rs1236881045	3031	dbSNP
rs941298459	3032	dbSNP
rs1038203553	3043	dbSNP
rs1293737289	3046	dbSNP
rs1234925249	3057	dbSNP
rs182800817	3066	dbSNP
rs1287851164	3071	dbSNP
rs906554451	3073	dbSNP
rs144909049	3074	dbSNP
rs535093114	3079	dbSNP
rs1460158269	3092	dbSNP
rs558286853	3093	dbSNP
rs1417520848	3105	dbSNP
rs993899486	3106	dbSNP
rs140677590	3115	dbSNP
rs1259795160	3118	dbSNP
rs1204612996	3125	dbSNP
rs1005803091	3128	dbSNP
rs1273766891	3130	dbSNP
rs1342622804	3131	dbSNP
rs537484445	3136	dbSNP
rs1012335612	3149	dbSNP
rs1023851090	3150	dbSNP
rs1292432490	3155	dbSNP
rs1016830197	3157	dbSNP
rs968700756	3160	dbSNP
rs752782942	3165	dbSNP
rs1031113151	3166	dbSNP
rs1278928397	3171	dbSNP
rs956892382	3173	dbSNP
rs976114169	3174	dbSNP
rs972655547	3176	dbSNP
rs116307275	3177	dbSNP
rs1460327611	3181	dbSNP
rs1394295278	3183	dbSNP
rs1168824960	3184	dbSNP
rs1463769868	3187	dbSNP
rs574281333	3199	dbSNP
rs536839336	3200	dbSNP
rs187402670	3201	dbSNP
rs764596326	3205	dbSNP
rs941246059	3206	dbSNP
rs1467079444	3207	dbSNP
rs373570249	3212	dbSNP
rs1428132499	3217	dbSNP
rs1196136957	3219	dbSNP
rs1038319215	3222	dbSNP
rs1249266644	3223	dbSNP
rs754145613	3226	dbSNP
rs1054375891	3227	dbSNP
rs758104454	3237	dbSNP
rs1304987546	3255	dbSNP
rs1439394726	3259	dbSNP
rs1351195198	3260	dbSNP
rs1327597313	3262	dbSNP
rs929810049	3262	dbSNP
rs780033602	3263	dbSNP
rs10151514	3266	dbSNP
rs1393528371	3269	dbSNP
rs1394697089	3271	dbSNP
rs945591340	3273	dbSNP
rs60502298	3278	dbSNP
rs1329092531	3286	dbSNP
rs11847752	3287	dbSNP
rs1435553842	3305	dbSNP
rs1397037345	3310	dbSNP
rs1171809879	3320	dbSNP
rs1232236395	3320	dbSNP
rs772588202	3326	dbSNP
rs116051996	3327	dbSNP
rs34899014	3330	dbSNP
rs1439357641	3334	dbSNP
rs11847787	3338	dbSNP
rs114867894	3342	dbSNP
rs939339628	3348	dbSNP
rs1348121037	3349	dbSNP
rs903544878	3353	dbSNP
rs1055174168	3354	dbSNP
rs1001052356	3358	dbSNP
rs754979639	3372	dbSNP
rs1031231086	3374	dbSNP
rs1005358658	3375	dbSNP
rs1444917167	3376	dbSNP
rs879036141	3377	dbSNP
rs956840835	3378	dbSNP
rs1433155642	3385	dbSNP
rs112500183	3386	dbSNP
rs1030376025	3388	dbSNP
rs1311240677	3389	dbSNP
rs1434218008	3393	dbSNP
rs1408737087	3396	dbSNP
rs1159136044	3399	dbSNP
rs953580960	3402	dbSNP
rs986261839	3409	dbSNP
rs909187170	3410	dbSNP
rs963392053	3413	dbSNP
rs1371202814	3414	dbSNP
rs548999715	3415	dbSNP
rs758191744	3415	dbSNP
rs918516872	3416	dbSNP
rs929757751	3418	dbSNP
rs1291913829	3421	dbSNP
rs543077814	3421	dbSNP
rs1226046463	3425	dbSNP
rs1288174124	3432	dbSNP
rs1355242717	3436	dbSNP
rs1357714001	3439	dbSNP
rs1291681998	3441	dbSNP
rs1414383002	3448	dbSNP
rs955008729	3452	dbSNP
rs563581953	3455	dbSNP
rs1402423602	3456	dbSNP
rs1326319349	3457	dbSNP
rs1372928406	3458	dbSNP
rs755573663	3459	dbSNP
rs1419691315	3460	dbSNP
rs61992958	3460	dbSNP
rs1162493307	3461	dbSNP
rs1195281217	3461	dbSNP
rs1214791935	3461	dbSNP
rs1217284650	3461	dbSNP
rs1227999891	3461	dbSNP
rs1259810645	3461	dbSNP
rs1268087250	3461	dbSNP
rs1271654084	3461	dbSNP
rs1272094299	3461	dbSNP
rs1319828910	3461	dbSNP
rs1351418960	3461	dbSNP
rs1362892165	3461	dbSNP
rs1396503838	3461	dbSNP
rs1404451721	3461	dbSNP
rs1419818839	3461	dbSNP
rs1428755905	3461	dbSNP
rs1444730901	3461	dbSNP
rs1461885329	3461	dbSNP
rs1491226511	3461	dbSNP
rs775439859	3461	dbSNP
rs1194875137	3462	dbSNP
rs1271714999	3462	dbSNP
rs12717676	3462	dbSNP
rs1470196058	3462	dbSNP
rs36009825	3462	dbSNP
rs61088841	3462	dbSNP
rs869080785	3462	dbSNP
rs1225644595	3463	dbSNP
rs1221321955	3464	dbSNP
rs1296443138	3466	dbSNP
rs1342492906	3471	dbSNP
rs1228932838	3472	dbSNP
rs1263238478	3473	dbSNP
rs1308405002	3476	dbSNP
rs1488430224	3477	dbSNP
rs1275383306	3485	dbSNP
rs1212963921	3488	dbSNP
rs1341622330	3488	dbSNP
rs1210969468	3489	dbSNP
rs1441604120	3490	dbSNP
rs1255208566	3494	dbSNP
rs1373071660	3494	dbSNP
rs985533321	3494	dbSNP
rs1463845625	3497	dbSNP
rs1188116077	3499	dbSNP
rs1017994969	3506	dbSNP
rs1354832777	3507	dbSNP
rs1430565100	3508	dbSNP
rs1162767246	3509	dbSNP
rs1427418817	3510	dbSNP
rs1389056524	3512	dbSNP
rs1173690029	3513	dbSNP
rs1251713712	3513	dbSNP
rs1455155731	3513	dbSNP
rs1191053586	3514	dbSNP
rs1481170149	3515	dbSNP
rs957334946	3516	dbSNP
rs917790822	3519	dbSNP
rs1198010786	3520	dbSNP
rs1236616786	3520	dbSNP
rs1345767343	3520	dbSNP
rs947781064	3521	dbSNP
rs1373871800	3523	dbSNP
rs1044842141	3526	dbSNP
rs1407664124	3533	dbSNP
rs372137822	3537	dbSNP
rs548293133	3537	dbSNP
rs1432607432	3539	dbSNP
rs903504895	3543	dbSNP
rs1436044351	3544	dbSNP
rs1375368435	3546	dbSNP
rs1176043354	3548	dbSNP
rs978303628	3550	dbSNP
rs867203572	3558	dbSNP
rs1410676843	3561	dbSNP
rs928201891	3564	dbSNP
rs1482907121	3571	dbSNP
rs1258528833	3577	dbSNP
rs1362221627	3584	dbSNP
rs939308431	3601	dbSNP
rs1270803754	3605	dbSNP
rs1055550245	3612	dbSNP
rs895178133	3613	dbSNP
rs1209384321	3616	dbSNP
rs1317420774	3617	dbSNP
rs1000500234	3619	dbSNP
rs1226376586	3625	dbSNP
rs1052601717	3629	dbSNP
rs1383615496	3630	dbSNP
rs1309883845	3631	dbSNP
rs1320592668	3632	dbSNP
rs780783838	3634	dbSNP
rs1444146894	3635	dbSNP
rs1234391170	3640	dbSNP
rs892721456	3641	dbSNP
rs1275625825	3648	dbSNP
rs1454810795	3649	dbSNP
rs1038493363	3650	dbSNP
rs1157538495	3659	dbSNP
rs1472472476	3661	dbSNP
rs896986177	3667	dbSNP
rs993969581	3667	dbSNP
rs747608908	3669	dbSNP
rs138334082	3673	dbSNP
rs891055511	3675	dbSNP
rs1006837281	3681	dbSNP
rs1249110975	3682	dbSNP
rs1018338480	3696	dbSNP
rs1486865985	3702	dbSNP
rs957098198	3702	dbSNP
rs1180352024	3716	dbSNP
rs11847805	3717	dbSNP
rs1188361298	3742	dbSNP
rs1424507578	3749	dbSNP
rs1030904212	3761	dbSNP
rs1234795417	3764	dbSNP
rs549280599	3766	dbSNP
rs144424615	3772	dbSNP
rs1311509617	3773	dbSNP
rs528304923	3777	dbSNP
rs1419900727	3780	dbSNP
rs1008033450	3790	dbSNP
rs559066758	3791	dbSNP
rs551896704	3800	dbSNP
rs1158132022	3801	dbSNP
rs571816794	3804	dbSNP
rs1345575008	3807	dbSNP
rs747431403	3809	dbSNP
rs1395761611	3812	dbSNP
rs1454958998	3821	dbSNP
rs930662434	3828	dbSNP
rs972063735	3829	dbSNP
rs1456667447	3831	dbSNP
rs928175536	3832	dbSNP
rs1377746203	3833	dbSNP
rs1430392811	3839	dbSNP
rs939587347	3842	dbSNP
rs1026360031	3847	dbSNP
rs991111944	3848	dbSNP
rs1464365354	3849	dbSNP
rs951266757	3855	dbSNP
rs537432957	3856	dbSNP
rs1349176655	3860	dbSNP
rs941405595	3861	dbSNP
rs917722665	3866	dbSNP
rs1319110885	3867	dbSNP
rs947929384	3868	dbSNP
rs1227630360	3875	dbSNP
rs1294761566	3876	dbSNP
rs980900311	3876	dbSNP
rs749012265	3878	dbSNP
rs1435074120	3880	dbSNP
rs1208233930	3883	dbSNP
rs1328466149	3885	dbSNP
rs550734342	3887	dbSNP
rs528805777	3893	dbSNP
rs1052047690	3894	dbSNP
rs567669200	3896	dbSNP
rs1424871701	3903	dbSNP
rs1007217150	3912	dbSNP
rs1039657842	3921	dbSNP
rs892161867	3923	dbSNP
rs1454731375	3924	dbSNP
rs1483723513	3936	dbSNP
rs1200834776	3939	dbSNP
rs192254509	3944	dbSNP
rs377445550	3945	dbSNP
rs146596290	3950	dbSNP
rs573089078	3952	dbSNP
rs1007736077	3959	dbSNP
rs76325844	3961	dbSNP
rs755253033	3962	dbSNP
rs1408387825	3965	dbSNP
rs993617614	3975	dbSNP
rs1402252517	3983	dbSNP
rs1002655999	3986	dbSNP
rs115129088	3987	dbSNP
rs960089993	3997	dbSNP
rs960944893	3998	dbSNP
rs141436531	4006	dbSNP
rs571514008	4010	dbSNP
rs1368975431	4013	dbSNP
rs969593478	4014	dbSNP
rs1307611626	4016	dbSNP
rs1435426927	4017	dbSNP
rs370583456	4021	dbSNP
rs925156140	4022	dbSNP
rs1476997899	4026	dbSNP
rs1376897979	4034	dbSNP
rs563108683	4039	dbSNP
rs776041754	4041	dbSNP
rs796418229	4041	dbSNP
rs1473427197	4042	dbSNP
rs1409681965	4046	dbSNP
rs1203922947	4047	dbSNP
rs936412836	4050	dbSNP
rs1280117271	4054	dbSNP
rs1375921377	4056	dbSNP
rs987875694	4057	dbSNP
rs760655382	4062	dbSNP
rs930042858	4063	dbSNP
rs933014691	4069	dbSNP
rs1052415596	4072	dbSNP
rs764281426	4077	dbSNP
rs1348852930	4078	dbSNP
rs1213304177	4079	dbSNP
rs1287982061	4080	dbSNP
rs912375547	4081	dbSNP
rs889380122	4082	dbSNP
rs1332239006	4083	dbSNP
rs943659505	4088	dbSNP
rs573584605	4089	dbSNP
rs899359024	4095	dbSNP
rs753975726	4101	dbSNP
rs1458629137	4105	dbSNP
rs1026417025	4108	dbSNP
rs1203671028	4133	dbSNP
rs1475310531	4143	dbSNP
rs1238748188	4145	dbSNP
rs895774490	4147	dbSNP
rs1441296828	4148	dbSNP
rs1014263391	4150	dbSNP
rs1233362553	4150	dbSNP
rs1471143300	4151	dbSNP
rs1189245812	4152	dbSNP
rs1039986104	4153	dbSNP
rs1025272881	4156	dbSNP
rs1267888735	4162	dbSNP
rs1234177529	4163	dbSNP
rs969328788	4179	dbSNP
rs749542823	4181	dbSNP
rs1041393336	4186	dbSNP
rs1282602671	4191	dbSNP
rs902876335	4197	dbSNP
rs542517287	4207	dbSNP
rs540332824	4210	dbSNP
rs1032117759	4216	dbSNP
rs961127365	4220	dbSNP
rs1437179584	4230	dbSNP
rs559726282	4231	dbSNP
rs987821405	4232	dbSNP
rs58802954	4233	dbSNP
rs1415552641	4239	dbSNP
rs866383302	4244	dbSNP
rs1161029994	4250	dbSNP
rs954489377	4255	dbSNP
rs1042890	4256	dbSNP
rs565365091	4258	dbSNP
rs567460031	4265	dbSNP
rs1191127380	4266	dbSNP
rs943623085	4267	dbSNP
rs1435017668	4268	dbSNP
rs1037980269	4282	dbSNP
rs920735680	4284	dbSNP
rs951416751	4288	dbSNP
rs929471263	4289	dbSNP
rs908147142	4292	dbSNP
rs530876498	4299	dbSNP
rs1227946623	4300	dbSNP
rs912649051	4308	dbSNP
rs1299875173	4311	dbSNP
rs942503278	4316	dbSNP
rs895902475	4318	dbSNP
rs1319757216	4320	dbSNP
rs1436941861	4321	dbSNP
rs1014792744	4323	dbSNP
rs878913444	4331	dbSNP
rs1351348521	4332	dbSNP
rs1044393569	4339	dbSNP
rs1334286433	4348	dbSNP
rs1321247317	4350	dbSNP
rs551079006	4352	dbSNP
rs1215209144	4356	dbSNP
rs1169915393	4365	dbSNP
rs1447079993	4373	dbSNP
rs536333074	4374	dbSNP
rs1032234157	4381	dbSNP
rs536687543	4389	dbSNP
rs1194743589	4394	dbSNP
rs957833877	4400	dbSNP
rs947270282	4401	dbSNP
rs1042892	4405	dbSNP
rs1009360849	4408	dbSNP
rs1021249230	4411	dbSNP
rs1438583159	4416	dbSNP
rs1252077982	4420	dbSNP
rs1226312322	4422	dbSNP
rs76471599	4432	dbSNP
rs902845056	4439	dbSNP
rs987657233	4442	dbSNP
rs1369551579	4445	dbSNP
rs566850071	4448	dbSNP
rs1272827825	4451	dbSNP
rs964390690	4452	dbSNP
rs938336541	4456	dbSNP
rs973620790	4459	dbSNP
rs894243791	4462	dbSNP
rs1012800777	4469	dbSNP
rs1023785699	4476	dbSNP
rs1177508187	4482	dbSNP
rs898699239	4490	dbSNP
rs1423565915	4496	dbSNP
rs1191001155	4497	dbSNP
rs920852210	4500	dbSNP
rs929420481	4501	dbSNP
rs1421037650	4505	dbSNP
rs1404022976	4508	dbSNP
rs1281128856	4525	dbSNP
rs1047922024	4530	dbSNP
rs116403280	4532	dbSNP
rs950150220	4535	dbSNP
rs1218463080	4540	dbSNP
rs1044894656	4541	dbSNP
rs986780136	4552	dbSNP
rs1319009308	4554	dbSNP
rs905836752	4557	dbSNP
rs1000160459	4563	dbSNP
rs573126876	4565	dbSNP
rs755550032	4567	dbSNP
rs1009475586	4568	dbSNP
rs1175892363	4580	dbSNP
rs1458110373	4581	dbSNP
rs1020775211	4585	dbSNP
rs947239090	4588	dbSNP
rs1472371112	4592	dbSNP
rs890311528	4594	dbSNP
rs534926720	4597	dbSNP
rs532220309	4598	dbSNP
rs1254182446	4604	dbSNP
rs61992959	4607	dbSNP
rs1329689921	4608	dbSNP
rs1269751381	4612	dbSNP
rs1226241545	4635	dbSNP
rs1328069792	4636	dbSNP
rs1446000144	4647	dbSNP
rs1193456450	4648	dbSNP
rs150258571	4649	dbSNP
rs1302836159	4652	dbSNP
rs1471536128	4654	dbSNP
rs973066300	4655	dbSNP
rs1186662705	4666	dbSNP
rs1157373256	4669	dbSNP
rs1027362954	4671	dbSNP
rs557028635	4672	dbSNP
rs1042897	4687	dbSNP
rs1157380316	4696	dbSNP
rs1182954416	4697	dbSNP
rs11352547	4698	dbSNP
rs1328141533	4698	dbSNP
rs1465273950	4698	dbSNP
rs796209232	4698	dbSNP
rs1265674960	4700	dbSNP
rs1246520019	4709	dbSNP
rs200272385	4710	dbSNP
rs1319475215	4721	dbSNP
rs1388383436	4721	dbSNP
rs1401435195	4723	dbSNP
rs984136748	4725	dbSNP
rs917401984	4727	dbSNP
rs1447365234	4731	dbSNP
rs950277925	4736	dbSNP
rs542654565	4737	dbSNP
rs200760700	4743	dbSNP
rs746224363	4745	dbSNP
rs995634358	4746	dbSNP
rs1235072095	4752	dbSNP
rs1265933848	4754	dbSNP
rs1349724365	4758	dbSNP
rs1205304686	4760	dbSNP
rs1025826186	4768	dbSNP
rs1054379828	4774	dbSNP
rs573210257	4775	dbSNP
rs1440375507	4778	dbSNP
rs1008459995	4779	dbSNP
rs1446268137	4779	dbSNP
rs945279540	4781	dbSNP
rs1042713376	4782	dbSNP
rs772480355	4785	dbSNP
rs1343596673	4787	dbSNP
rs1296064969	4789	dbSNP
rs975518084	4791	dbSNP
rs775952028	4792	dbSNP
rs1303831985	4793	dbSNP
rs1009153842	4794	dbSNP
rs184737326	4796	dbSNP
rs968501069	4798	dbSNP
rs1308789378	4803	dbSNP
rs1431716281	4804	dbSNP
rs563458842	4810	dbSNP
rs565047854	4816	dbSNP
rs924493618	4817	dbSNP
rs1166716810	4818	dbSNP
rs1475027088	4819	dbSNP
rs370652639	4831	dbSNP
rs1363544052	4832	dbSNP
rs1267739568	4833	dbSNP
rs1205358164	4839	dbSNP
rs375199899	4841	dbSNP
rs11449512	4842	dbSNP
rs1271818657	4842	dbSNP
rs397757742	4842	dbSNP
rs1195778141	4844	dbSNP
rs1160705507	4853	dbSNP
rs61993676	4854	dbSNP
rs138752520	4858	dbSNP
rs148926813	4859	dbSNP
rs1037416121	4863	dbSNP
rs920361372	4864	dbSNP
rs931451956	4865	dbSNP
rs950386668	4866	dbSNP
rs1411890865	4882	dbSNP
rs1348754569	4885	dbSNP
rs546621344	4890	dbSNP
rs189088692	4895	dbSNP
rs9291	4908	dbSNP
rs1174184003	4910	dbSNP
rs552454278	4917	dbSNP
rs971551075	4919	dbSNP
rs899798915	4920	dbSNP
rs1182498923	4922	dbSNP
rs879069457	4926	dbSNP
rs997258895	4927	dbSNP
rs569312007	4932	dbSNP
rs1239461410	4935	dbSNP
rs927501922	4940	dbSNP
rs936076195	4941	dbSNP
rs968804731	4942	dbSNP
rs998968779	4955	dbSNP
rs1258884565	4958	dbSNP
rs1218986611	4961	dbSNP
rs990219476	4966	dbSNP
rs538472434	4967	dbSNP
rs1342423161	4972	dbSNP
rs946050081	4973	dbSNP
rs1279151595	4979	dbSNP
rs992724501	4980	dbSNP
rs10830	4988	dbSNP
rs1209726606	4988	dbSNP
rs1342284017	5001	dbSNP
rs1042270441	5010	dbSNP
rs915815331	5026	dbSNP
rs969726670	5029	dbSNP
rs1405141831	5041	dbSNP
rs1159656571	5043	dbSNP
rs890370489	5049	dbSNP
rs1280335436	5053	dbSNP
rs1486384673	5057	dbSNP
rs11427	5058	dbSNP
rs765552640	5059	dbSNP
rs1157572400	5060	dbSNP
rs1472873580	5075	dbSNP
rs1250411326	5076	dbSNP
rs1438942944	5081	dbSNP
rs567383374	5090	dbSNP
rs920289208	5139	dbSNP
rs1461246643	5142	dbSNP
rs1184425003	5144	dbSNP
rs929037728	5150	dbSNP
rs900363833	5157	dbSNP
rs1376294287	5161	dbSNP
rs536240211	5163	dbSNP
rs1453937172	5165	dbSNP
rs1229093843	5174	dbSNP
rs750732827	5189	dbSNP

- 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.

- Nucleic acids research, 2016

MicroRNAs (miRs) have emerged as key biological effectors in human health and disease. These small noncoding RNAs are incorporated into Argonaute (Ago) proteins, where they direct post-transcriptional gene silencing via base-pairing with target transcripts. Although miRs have become intriguing biological entities and attractive therapeutic targets, the translational impacts of miR research remain limited by a paucity of empirical miR targeting data, particularly in human primary tissues. Here, to improve our understanding of the diverse roles miRs play in cardiovascular function and disease, we applied high-throughput methods to globally profile miR:target interactions in human heart tissues. We deciphered Ago2:RNA interactions using crosslinking immunoprecipitation coupled with high-throughput sequencing (HITS-CLIP) to generate the first transcriptome-wide map of miR targeting events in human myocardium, detecting 4000 cardiac Ago2 binding sites across >2200 target transcripts. Our initial exploration of this interactome revealed an abundance of miR target sites in gene coding regions, including several sites pointing to new miR-29 functions in regulating cardiomyocyte calcium, growth and metabolism. Also, we uncovered several clinically-relevant interactions involving common genetic variants that alter miR targeting events in cardiomyopathy-associated genes. Overall, these data provide a critical resource for bolstering translational miR research in heart, and likely beyond.