>UBE2S|NM_014501|3'UTR
   1 TGGGCTCTCTTCCTCCTTCCACCGTGACCCCAACCTCTCCTGTCCCCTCCCTCCAACTCTGTCTCTAAGTTATTTAAATT
  81 ATGGCTGGGGTCGGGGAGGGTACAGGGGGCACTGGGACCTGGATTTGTTTTTCTAAATAAAGTTGGAAAAGCAGAAAAAA
 161 AAAAAAAAAA

ID	Duplex structure	Position	Score	MFE
1	miRNA 3' ugacaGACAGAGUC-UUGGGGUc 5' || | | | :|||||| Target 5' tcctcCTTCCACCGTGACCCCAa 3'	11 - 33	129.00	-10.80
2	miRNA 3' ugACA---GACAGAGUCUUGGGGUc 5' ||| || ||| |||:|:: Target 5' ccTGTCCCCTCCCTC-CAACTCTGt 3'	39 - 62	103.00	-10.86
3	miRNA 3' ugacagacaGAGUCUUGGGguc 5' || :|:|||: Target 5' cagggggcaCT-GGGACCTgga 3'	103 - 123	76.00	-9.60

Mutant ID	Mutant Position	Mutant Source
COSN30467544	7	COSMIC
COSN17983632	101	COSMIC
COSN24854185	115	COSMIC
COSN31547341	140	COSMIC
COSN1218982	237	COSMIC
COSN1218981	262	COSMIC
COSN18939932	272	COSMIC
COSN24430455	405	COSMIC
COSN4968369	756	COSMIC
COSN28465485	1142	COSMIC
COSN21086114	1149	COSMIC
COSN20130255	1293	COSMIC
COSN20135074	1294	COSMIC
COSN29301030	1526	COSMIC
COSN22247583	1544	COSMIC

Mutant ID	Mutant Position	Mutant Source
rs1215069589	1	dbSNP
rs778022859	2	dbSNP
rs1292351637	3	dbSNP
rs758160767	4	dbSNP
rs752397400	6	dbSNP
rs1220465770	7	dbSNP
rs1266273146	9	dbSNP
rs769578635	11	dbSNP
rs765091710	12	dbSNP
rs759322403	15	dbSNP
rs1382365751	16	dbSNP
rs983355396	18	dbSNP
rs950506715	22	dbSNP
rs765970088	24	dbSNP
rs536255941	25	dbSNP
rs772966489	28	dbSNP
rs771808441	29	dbSNP
rs761547344	30	dbSNP
rs775660863	33	dbSNP
rs1462668252	34	dbSNP
rs542371434	39	dbSNP
rs1213770880	40	dbSNP
rs1387263433	41	dbSNP
rs746357955	44	dbSNP
rs781707829	46	dbSNP
rs770980928	49	dbSNP
rs1376806879	50	dbSNP
rs10402826	51	dbSNP
rs1465808330	61	dbSNP
rs954783281	61	dbSNP
rs1207032791	67	dbSNP
rs1287429434	67	dbSNP
rs1031537372	74	dbSNP
rs1012511371	81	dbSNP
rs1217970491	89	dbSNP
rs191733596	90	dbSNP
rs186864699	92	dbSNP
rs769031848	93	dbSNP
rs1332212586	94	dbSNP
rs1156498325	96	dbSNP
rs373350101	97	dbSNP
rs1245955746	108	dbSNP
rs543343459	115	dbSNP
rs894509583	122	dbSNP
rs1057437561	132	dbSNP
rs1041748378	146	dbSNP
rs947425139	149	dbSNP
rs914660436	152	dbSNP
rs1437904737	159	dbSNP
rs577897404	174	dbSNP
rs557441663	177	dbSNP
rs1276557153	178	dbSNP
rs534629586	183	dbSNP
rs529789142	184	dbSNP
rs756313950	186	dbSNP
rs976740441	187	dbSNP
rs1458187710	188	dbSNP
rs572132762	189	dbSNP
rs910257314	192	dbSNP
rs987533491	194	dbSNP
rs1372295852	195	dbSNP
rs962275210	197	dbSNP
rs1174192343	199	dbSNP
rs1166578770	202	dbSNP
rs1451239204	210	dbSNP
rs112131960	211	dbSNP
rs1407791179	211	dbSNP
rs1014506968	215	dbSNP
rs1307137020	217	dbSNP
rs1449424812	220	dbSNP
rs1336623529	221	dbSNP
rs984432470	223	dbSNP
rs1273216986	227	dbSNP
rs1210093552	243	dbSNP
rs555506572	244	dbSNP
rs968553388	249	dbSNP
rs1021456993	256	dbSNP
rs1249986769	257	dbSNP
rs1231142406	260	dbSNP
rs1340594274	260	dbSNP
rs140788122	260	dbSNP
rs1013030189	264	dbSNP
rs1251648844	270	dbSNP
rs767920428	274	dbSNP
rs567853643	277	dbSNP
rs1012025714	280	dbSNP
rs1453283381	287	dbSNP
rs1193663746	290	dbSNP
rs896300430	291	dbSNP
rs1034898919	292	dbSNP
rs887090197	294	dbSNP
rs999409826	296	dbSNP
rs1427709740	298	dbSNP
rs1167786692	299	dbSNP
rs369651553	306	dbSNP
rs796535326	306	dbSNP
rs902445329	308	dbSNP
rs1391053526	316	dbSNP
rs1041717299	320	dbSNP
rs1330681280	320	dbSNP
rs1305949953	323	dbSNP
rs10403361	329	dbSNP
rs1228283169	331	dbSNP
rs1252316255	332	dbSNP
rs1371063328	334	dbSNP
rs1341904651	336	dbSNP
rs537319260	337	dbSNP
rs1467721743	338	dbSNP
rs893167115	338	dbSNP
rs112322456	339	dbSNP
rs1447648874	341	dbSNP
rs1192381581	343	dbSNP
rs1373512132	343	dbSNP
rs1476276430	345	dbSNP
rs1378863331	347	dbSNP
rs560899600	350	dbSNP
rs932127639	352	dbSNP
rs1199056956	355	dbSNP
rs1390326890	355	dbSNP
rs1462133014	360	dbSNP
rs1328061304	376	dbSNP
rs1386527318	380	dbSNP
rs1435095738	381	dbSNP
rs1296925325	383	dbSNP
rs571927623	384	dbSNP
rs1243111108	386	dbSNP
rs1283943633	399	dbSNP
rs551449905	408	dbSNP
rs1040525048	415	dbSNP
rs933000830	416	dbSNP
rs528474283	418	dbSNP
rs559374045	427	dbSNP
rs968605292	434	dbSNP
rs1021509358	439	dbSNP
rs1448617388	441	dbSNP
rs1185189926	445	dbSNP
rs1416865030	447	dbSNP
rs549062595	454	dbSNP
rs371023285	455	dbSNP
rs991314927	459	dbSNP
rs916282547	460	dbSNP
rs1289482732	461	dbSNP
rs1275500073	463	dbSNP
rs370754289	468	dbSNP
rs11669732	472	dbSNP
rs960490606	475	dbSNP
rs879836140	481	dbSNP
rs113207411	486	dbSNP
rs999377348	487	dbSNP
rs1025580541	493	dbSNP
rs1290496468	512	dbSNP
rs1378272066	516	dbSNP
rs538388721	517	dbSNP
rs115201589	518	dbSNP
rs1260768843	519	dbSNP
rs564414261	520	dbSNP
rs764971677	522	dbSNP
rs761760162	523	dbSNP
rs1412697505	529	dbSNP
rs1256623548	532	dbSNP
rs1485879345	537	dbSNP
rs1010860418	538	dbSNP
rs1189730775	543	dbSNP
rs1249930793	549	dbSNP
rs893122326	550	dbSNP
rs1050449174	553	dbSNP
rs540620810	554	dbSNP
rs1465045461	557	dbSNP
rs1452475087	563	dbSNP
rs1409254928	571	dbSNP
rs1417038119	571	dbSNP
rs1306513823	575	dbSNP
rs1348281547	595	dbSNP
rs1183940498	603	dbSNP
rs776597292	606	dbSNP
rs1307155538	607	dbSNP
rs1051963246	608	dbSNP
rs901942249	611	dbSNP
rs933071820	614	dbSNP
rs146428513	623	dbSNP
rs535524061	626	dbSNP
rs1444630892	628	dbSNP
rs1272186989	630	dbSNP
rs1041403070	632	dbSNP
rs947321139	633	dbSNP
rs546524341	644	dbSNP
rs753593723	650	dbSNP
rs914503109	663	dbSNP
rs760242644	664	dbSNP
rs958797771	666	dbSNP
rs1292429835	678	dbSNP
rs1298397093	682	dbSNP
rs1445629838	685	dbSNP
rs928472369	693	dbSNP
rs773069167	696	dbSNP
rs1371703625	697	dbSNP
rs145533320	705	dbSNP
rs1025633028	710	dbSNP
rs560859618	711	dbSNP
rs182092408	712	dbSNP
rs140397330	722	dbSNP
rs927679455	723	dbSNP
rs201185580	727	dbSNP
rs1161795609	730	dbSNP
rs1456009024	734	dbSNP
rs891318433	739	dbSNP
rs771224810	742	dbSNP
rs1419343153	744	dbSNP
rs1051255362	764	dbSNP
rs1474007742	765	dbSNP
rs191062366	768	dbSNP
rs1022174955	769	dbSNP
rs1459529405	775	dbSNP
rs1463546604	779	dbSNP
rs563410077	780	dbSNP
rs1010786896	787	dbSNP
rs1249995749	792	dbSNP
rs953993249	794	dbSNP
rs1468197925	795	dbSNP
rs535032330	797	dbSNP
rs372871268	801	dbSNP
rs1226374005	803	dbSNP
rs1358245150	811	dbSNP
rs1361131786	814	dbSNP
rs369442269	818	dbSNP
rs1041455919	822	dbSNP
rs914219493	826	dbSNP
rs151232228	827	dbSNP
rs901866035	831	dbSNP
rs1040424233	833	dbSNP
rs541011136	838	dbSNP
rs1004958700	840	dbSNP
rs1242068566	843	dbSNP
rs1321968382	852	dbSNP
rs1435238149	853	dbSNP
rs981288173	855	dbSNP
rs1393252398	856	dbSNP
rs1321203511	865	dbSNP
rs529319721	872	dbSNP
rs570150054	878	dbSNP
rs756260583	893	dbSNP
rs1049223170	894	dbSNP
rs1315567149	902	dbSNP
rs1344581320	910	dbSNP
rs1414982320	916	dbSNP
rs918672628	917	dbSNP
rs142163329	919	dbSNP
rs974104018	923	dbSNP
rs369595627	924	dbSNP
rs962698756	935	dbSNP
rs1018218088	936	dbSNP
rs1007577327	938	dbSNP
rs1392637875	946	dbSNP
rs1222169640	947	dbSNP
rs1283611835	955	dbSNP
rs1318110831	960	dbSNP
rs955647945	962	dbSNP
rs1030279043	963	dbSNP
rs748296319	966	dbSNP
rs146947246	968	dbSNP
rs999708760	969	dbSNP
rs1468127694	970	dbSNP
rs1475968608	970	dbSNP
rs1406587335	977	dbSNP
rs115386352	982	dbSNP
rs1373486965	999	dbSNP
rs1433890974	1000	dbSNP
rs1313219103	1005	dbSNP
rs79070871	1007	dbSNP
rs1453062081	1012	dbSNP
rs1055808884	1013	dbSNP
rs1279108536	1020	dbSNP
rs781436050	1025	dbSNP
rs939016660	1032	dbSNP
rs1011315198	1035	dbSNP
rs1204262259	1037	dbSNP
rs1451340947	1038	dbSNP
rs1347744506	1039	dbSNP
rs1212102371	1044	dbSNP
rs1282890798	1064	dbSNP
rs1339937806	1066	dbSNP
rs1179214827	1067	dbSNP
rs1470209071	1068	dbSNP
rs541321980	1069	dbSNP
rs977832680	1072	dbSNP
rs1055460218	1081	dbSNP
rs945108335	1083	dbSNP
rs1228430903	1086	dbSNP
rs915041772	1088	dbSNP
rs1377044103	1089	dbSNP
rs10408525	1092	dbSNP
rs954077353	1095	dbSNP
rs1028225499	1101	dbSNP
rs1046019999	1102	dbSNP
rs977104437	1103	dbSNP
rs966065189	1104	dbSNP
rs1235643915	1105	dbSNP
rs1337856109	1106	dbSNP
rs1195530247	1107	dbSNP
rs1271877042	1108	dbSNP
rs1018941067	1111	dbSNP
rs1250572594	1111	dbSNP
rs564905881	1111	dbSNP
rs1453793496	1113	dbSNP
rs766862841	1115	dbSNP
rs1428261893	1117	dbSNP
rs545086505	1121	dbSNP
rs578056416	1127	dbSNP
rs886533748	1128	dbSNP
rs78531788	1129	dbSNP
rs1324040347	1130	dbSNP
rs1423173980	1135	dbSNP
rs541872311	1137	dbSNP
rs955523192	1139	dbSNP
rs576174802	1140	dbSNP
rs765057103	1141	dbSNP
rs868722123	1142	dbSNP
rs73932627	1144	dbSNP
rs1339718729	1147	dbSNP
rs1220071923	1148	dbSNP
rs377270709	1150	dbSNP
rs1276642694	1151	dbSNP
rs906157422	1154	dbSNP
rs1042081348	1157	dbSNP
rs1275878191	1159	dbSNP
rs1220515682	1160	dbSNP
rs1373413211	1164	dbSNP
rs892882190	1165	dbSNP
rs1163063326	1167	dbSNP
rs945077073	1180	dbSNP
rs1167146217	1181	dbSNP
rs1034479189	1185	dbSNP
rs915015072	1186	dbSNP
rs1319460989	1188	dbSNP
rs1328567055	1196	dbSNP
rs1001210042	1197	dbSNP
rs906838516	1200	dbSNP
rs989660990	1201	dbSNP
rs1287381210	1202	dbSNP
rs1348521205	1204	dbSNP
rs1204471253	1213	dbSNP
rs1262266457	1218	dbSNP
rs932490171	1219	dbSNP
rs528021529	1225	dbSNP
rs1185473924	1227	dbSNP
rs976695288	1228	dbSNP
rs965268765	1232	dbSNP
rs1309109952	1243	dbSNP
rs1038165202	1244	dbSNP
rs941484016	1249	dbSNP
rs1018868761	1253	dbSNP
rs73619637	1254	dbSNP
rs950742966	1260	dbSNP
rs753767993	1261	dbSNP
rs759011123	1262	dbSNP
rs1433280518	1267	dbSNP
rs1178288523	1269	dbSNP
rs1027725761	1277	dbSNP
rs73932626	1278	dbSNP
rs1314330398	1279	dbSNP
rs1407470533	1280	dbSNP
rs895313561	1291	dbSNP
rs1261266984	1298	dbSNP
rs966946473	1308	dbSNP
rs1180331490	1311	dbSNP
rs1022503461	1323	dbSNP
rs1471448974	1323	dbSNP
rs1034264880	1326	dbSNP
rs187632970	1327	dbSNP
rs760615043	1331	dbSNP
rs1248617978	1333	dbSNP
rs1418600735	1335	dbSNP
rs61280119	1339	dbSNP
rs959486701	1340	dbSNP
rs1034120250	1345	dbSNP
rs1042049831	1348	dbSNP
rs1001662719	1354	dbSNP
rs555307211	1355	dbSNP
rs766970817	1360	dbSNP
rs1467837773	1362	dbSNP
rs1304245276	1363	dbSNP
rs1235699523	1370	dbSNP
rs375485959	1376	dbSNP
rs1312285851	1384	dbSNP
rs994085521	1389	dbSNP
rs148671139	1391	dbSNP
rs897071148	1396	dbSNP
rs1267051333	1398	dbSNP
rs773926056	1399	dbSNP
rs1038217675	1407	dbSNP
rs1211915132	1419	dbSNP
rs1249864047	1420	dbSNP
rs932433089	1421	dbSNP
rs1226206874	1431	dbSNP
rs921068411	1447	dbSNP
rs570552554	1448	dbSNP
rs550782282	1452	dbSNP
rs1196506533	1459	dbSNP
rs1240085490	1460	dbSNP
rs73054989	1463	dbSNP
rs1193559897	1465	dbSNP
rs1289373668	1473	dbSNP
rs1435304325	1474	dbSNP
rs943929108	1476	dbSNP
rs1395854911	1479	dbSNP
rs1377591385	1480	dbSNP
rs62128216	1483	dbSNP
rs1401838892	1488	dbSNP
rs1437996436	1492	dbSNP
rs1448801626	1493	dbSNP
rs982692027	1503	dbSNP
rs1293147322	1509	dbSNP
rs1388005009	1519	dbSNP
rs1157140640	1526	dbSNP
rs1228420298	1527	dbSNP
rs562034124	1538	dbSNP
rs1332779849	1539	dbSNP
rs1049852461	1540	dbSNP
rs950710850	1542	dbSNP
rs1254217171	1544	dbSNP
rs1489737752	1551	dbSNP
rs920630396	1556	dbSNP
rs547752624	1557	dbSNP
rs1261454933	1558	dbSNP
rs557024067	1561	dbSNP
rs973471203	1562	dbSNP
rs1459443238	1568	dbSNP
rs1163542595	1570	dbSNP
rs1350447917	1577	dbSNP
rs959727130	1585	dbSNP
rs1413060630	1588	dbSNP
rs769087450	1592	dbSNP
rs368068175	1594	dbSNP
rs773843794	1595	dbSNP
rs1438504971	1598	dbSNP
rs1286966624	1603	dbSNP
rs1033821335	1615	dbSNP
rs1159581155	1620	dbSNP
rs1361013689	1630	dbSNP
rs570607995	1631	dbSNP
rs1423074677	1636	dbSNP
rs1400316865	1637	dbSNP
rs1280364094	1639	dbSNP
rs922665091	1642	dbSNP
rs115107153	1644	dbSNP
rs1324088817	1647	dbSNP
rs1214272787	1652	dbSNP
rs1483258789	1653	dbSNP
rs376606864	1658	dbSNP
rs116185341	1659	dbSNP
rs13343706	1660	dbSNP
rs1465954339	1661	dbSNP
rs1186673925	1663	dbSNP
rs1413877806	1665	dbSNP
rs1406533968	1669	dbSNP
rs989706106	1677	dbSNP
rs1268423577	1678	dbSNP
rs1244458136	1682	dbSNP
rs781284058	1682	dbSNP
rs959579140	1684	dbSNP
rs1353855829	1685	dbSNP
rs926771031	1688	dbSNP
rs1009858976	1692	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.

- 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.