>BCL2L1|NM_138578|3'UTR
   1 CCAGACACTGACCATCCACTCTACCCTCCCACCCCCTTCTCTGCTCCACCACATCCTCCGTCCAGCCGCCATTGCCACCA
  81 GGAGAACCACTACATGCAGCCCATGCCCACCTGCCCATCACAGGGTTGGGCCCAGATCTGGTCCCTTGCAGCTAGTTTTC
 161 TAGAATTTATCACACTTCTGTGAGACCCCCACACCTCAGTTCCCTTGGCCTCAGAATTCACAAAATTTCCACAAAATCTG
 241 TCCAAAGGAGGCTGGCAGGTATGGAAGGGTTTGTGGCTGGGGGCAGGAGGGCCCTACCTGATTGGTGCAACCCTTACCCC
 321 TTAGCCTCCCTGAAAATGTTTTTCTGCCAGGGAGCTTGAAAGTTTTCAGAACCTCTTCCCCAGAAAGGAGACTAGATTGC
 401 CTTTGTTTTGATGTTTGTGGCCTCAGAATTGATCATTTTCCCCCCACTCTCCCCACACTAACCTGGGTTCCCTTTCCTTC
 481 CATCCCTACCCCCTAAGAGCCATTTAGGGGCCACTTTTGACTAGGGATTCAGGCTGCTTGGGATAAAGATGCAAGGACCA
 561 GGACTCCCTCCTCACCTCTGGACTGGCTAGAGTCCTCACTCCCAGTCCAAATGTCCTCCAGAAGCCTCTGGCTAGAGGCC
 641 AGCCCCACCCAGGAGGGAGGGGGCTATAGCTACAGGAAGCACCCCATGCCAAAGCTAGGGTGGCCCTTGCAGTTCAGCAC
 721 CACCCTAGTCCCTTCCCCTCCCTGGCTCCCATGACCATACTGAGGGACCAACTGGGCCCAAGACAGATGCCCCAGAGCTG
 801 TTTATGGCCTCAGCTGCCTCACTTCCTACAAGAGCAGCCTGTGGCATCTTTGCCTTGGGCTGCTCCTCATGGTGGGTTCA
 881 GGGGACTCAGCCCTGAGGTGAAAGGGAGCTATCAGGAACAGCTATGGGAGCCCCAGGGTCTTCCCTACCTCAGGCAGGAA
 961 GGGCAGGAAGGAGAGCCTGCTGCATGGGGTGGGGTAGGGCTGACTAGAAGGGCCAGTCCTGCCTGGCCAGGCAGATCTGT
1041 GCCCCATGCCTGTCCAGCCTGGGCAGCCAGGCTGCCAAGGCCAGAGTGGCCTGGCCAGGAGCTCTTCAGGCCTCCCTCTC
1121 TCTTCTGCTCCACCCTTGGCCTGTCTCATCCCCAGGGGTCCCAGCCACCCCGGGCTCTCTGCTGTACATATTTGAGACTA
1201 GTTTTTATTCCTTGTGAAGATGATATACTATTTTTGTTAAGCGTGTCTGTATTTATGTGTGAGGAGCTGCTGGCTTGCAG
1281 TGCGCGTGCACGTGGAGAGCTGGTGCCCGGAGATTGGACGGCCTGATGCTCCCTCCCCTGCCCTGGTCCAGGGAAGCTGG
1361 CCGAGGGTCCTGGCTCCTGAGGGGCATCTGCCCCTCCCCCAACCCCCACCCCACACTTGTTCCAGCTCTTTGAAATAGTC
1441 TGTGTGAAGGTGAAAGTGCAGTTCAGTAATAAACTGTGTTTACTCAGTGAAAAAAAAAAAAAAAAAA

ID	Duplex structure	Position	Score	MFE
1	miRNA 3' cgAGGACAGG----UUGACCGAg 5' |||| || :||||||| Target 5' ccTCCTCACCTCTGGACTGGCTa 3'	567 - 589	151.00	-18.30
2	miRNA 3' cgAGGACAGGUUGACCGAg 5' ||| ||| |||||| Target 5' ctTCCCCTCC--CTGGCTc 3'	732 - 748	128.00	-17.70
3	miRNA 3' cgaggacagGUUGACCGAg 5' | :|||||| Target 5' tgtgaggagCTGCTGGCTt 3'	1258 - 1276	126.00	-10.00

Mutant ID	Mutant Position	Mutant Source
COSN30516422	12	COSMIC
COSN30153975	21	COSMIC
COSN30477605	36	COSMIC
COSN30591120	53	COSMIC
COSN30462607	59	COSMIC
COSN30496869	60	COSMIC
COSN24387724	68	COSMIC
COSN31501279	82	COSMIC
COSN31575007	84	COSMIC
COSN30181223	101	COSMIC
COSN30141227	146	COSMIC
COSN31573807	167	COSMIC
COSN31522982	174	COSMIC
COSN26676840	209	COSMIC
COSN15659943	294	COSMIC
COSN31515077	365	COSMIC
COSN32099867	390	COSMIC
COSN31489757	614	COSMIC
COSN24266726	628	COSMIC
COSN31528278	686	COSMIC
COSN1869589	930	COSMIC
COSN1869588	931	COSMIC
COSN30443842	987	COSMIC
COSN1247448	999	COSMIC
COSN31521406	1108	COSMIC
COSN30162334	1179	COSMIC
COSN22782259	1308	COSMIC
COSN5802493	1388	COSMIC
COSN28816001	1401	COSMIC
COSN14563075	1408	COSMIC
COSN28198296	1411	COSMIC
COSN21016819	1414	COSMIC

Mutant ID	Mutant Position	Mutant Source
rs781506995	6	dbSNP
rs757800093	8	dbSNP
rs751808059	11	dbSNP
rs1244379117	18	dbSNP
rs1246086266	19	dbSNP
rs764588065	19	dbSNP
rs1451150656	20	dbSNP
rs1216554681	25	dbSNP
rs754613701	26	dbSNP
rs753539518	27	dbSNP
rs765845311	35	dbSNP
rs1030657544	36	dbSNP
rs769154919	42	dbSNP
rs760138522	44	dbSNP
rs989916889	46	dbSNP
rs1243372307	48	dbSNP
rs1204774379	50	dbSNP
rs554584920	59	dbSNP
rs967769834	60	dbSNP
rs936677262	62	dbSNP
rs926738457	64	dbSNP
rs1401962362	67	dbSNP
rs980839387	68	dbSNP
rs969871111	79	dbSNP
rs1189056795	85	dbSNP
rs1266419496	98	dbSNP
rs1431216831	106	dbSNP
rs536243459	109	dbSNP
rs1022080146	114	dbSNP
rs1378390732	115	dbSNP
rs1456868565	116	dbSNP
rs1024061730	117	dbSNP
rs992719994	121	dbSNP
rs950656912	123	dbSNP
rs11550475	125	dbSNP
rs1366019003	128	dbSNP
rs1388859223	130	dbSNP
rs1439561988	133	dbSNP
rs1012013351	136	dbSNP
rs565690849	141	dbSNP
rs10861	152	dbSNP
rs1026219616	153	dbSNP
rs1227351857	169	dbSNP
rs1469106584	175	dbSNP
rs1035270230	180	dbSNP
rs1265066225	187	dbSNP
rs1219594547	188	dbSNP
rs994947146	189	dbSNP
rs1211389391	191	dbSNP
rs963075237	194	dbSNP
rs1003429993	202	dbSNP
rs1284972258	203	dbSNP
rs1180214408	207	dbSNP
rs886391008	208	dbSNP
rs1007283064	217	dbSNP
rs890642399	245	dbSNP
rs1239403000	248	dbSNP
rs1211982630	251	dbSNP
rs1459857115	254	dbSNP
rs1294518867	257	dbSNP
rs1370266387	264	dbSNP
rs1051910841	282	dbSNP
rs1047719179	288	dbSNP
rs1305403228	290	dbSNP
rs1441336995	293	dbSNP
rs1351870582	294	dbSNP
rs1009721157	298	dbSNP
rs1311981294	300	dbSNP
rs1366585869	302	dbSNP
rs1246818848	305	dbSNP
rs1291463957	314	dbSNP
rs770055952	320	dbSNP
rs34865640	331	dbSNP
rs1203367777	339	dbSNP
rs1254213489	342	dbSNP
rs1481030032	344	dbSNP
rs553661086	346	dbSNP
rs538525918	355	dbSNP
rs899244011	357	dbSNP
rs1345286656	360	dbSNP
rs1039065909	373	dbSNP
rs1390006220	378	dbSNP
rs1428216419	383	dbSNP
rs943451680	393	dbSNP
rs936669303	394	dbSNP
rs912030586	421	dbSNP
rs1301760882	425	dbSNP
rs1175975823	438	dbSNP
rs1230017270	439	dbSNP
rs1315641317	440	dbSNP
rs1341251098	441	dbSNP
rs1434147554	442	dbSNP
rs926610351	445	dbSNP
rs1308337516	446	dbSNP
rs1209595844	452	dbSNP
rs1267028357	456	dbSNP
rs1189703298	467	dbSNP
rs571443689	471	dbSNP
rs1045137100	472	dbSNP
rs988079245	477	dbSNP
rs1247914621	482	dbSNP
rs1264078411	484	dbSNP
rs745601479	485	dbSNP
rs924878889	492	dbSNP
rs549690378	493	dbSNP
rs1449547207	495	dbSNP
rs531471504	499	dbSNP
rs1351481436	502	dbSNP
rs1337370233	510	dbSNP
rs950573836	520	dbSNP
rs977738014	526	dbSNP
rs1364404340	533	dbSNP
rs967674861	537	dbSNP
rs1021986730	549	dbSNP
rs990531438	570	dbSNP
rs1282410414	574	dbSNP
rs959393524	575	dbSNP
rs919209235	576	dbSNP
rs1362322222	581	dbSNP
rs1034853217	586	dbSNP
rs567358983	588	dbSNP
rs1003826513	590	dbSNP
rs1314061712	599	dbSNP
rs886341110	604	dbSNP
rs112085564	610	dbSNP
rs527283085	611	dbSNP
rs994726961	617	dbSNP
rs1017242553	619	dbSNP
rs1190998136	624	dbSNP
rs756689819	628	dbSNP
rs1477903211	631	dbSNP
rs1190313769	639	dbSNP
rs1422598302	648	dbSNP
rs954468617	650	dbSNP
rs1362224634	656	dbSNP
rs1297091899	657	dbSNP
rs1455587429	659	dbSNP
rs116990630	660	dbSNP
rs1009778373	667	dbSNP
rs1376694397	674	dbSNP
rs1039018055	676	dbSNP
rs770813221	678	dbSNP
rs747000648	680	dbSNP
rs1377474392	686	dbSNP
rs905208400	703	dbSNP
rs1045066584	712	dbSNP
rs541725032	717	dbSNP
rs1051918296	718	dbSNP
rs934851519	724	dbSNP
rs1248781577	731	dbSNP
rs924784207	736	dbSNP
rs777327056	738	dbSNP
rs1410656541	743	dbSNP
rs558611326	746	dbSNP
rs1160265045	751	dbSNP
rs914879726	760	dbSNP
rs990927727	766	dbSNP
rs532665035	768	dbSNP
rs1367131681	769	dbSNP
rs1405843973	771	dbSNP
rs560997987	771	dbSNP
rs1348751835	777	dbSNP
rs1230279923	792	dbSNP
rs1280165152	806	dbSNP
rs1356304108	814	dbSNP
rs757916272	816	dbSNP
rs927726767	822	dbSNP
rs116239579	825	dbSNP
rs950577686	829	dbSNP
rs1026123997	832	dbSNP
rs1482879175	835	dbSNP
rs1222853389	837	dbSNP
rs1250570354	840	dbSNP
rs994679279	844	dbSNP
rs755868976	845	dbSNP
rs752260890	855	dbSNP
rs778372909	856	dbSNP
rs963297847	859	dbSNP
rs1254099326	865	dbSNP
rs1161332555	869	dbSNP
rs1386934123	872	dbSNP
rs543647087	876	dbSNP
rs1007995653	877	dbSNP
rs184626287	884	dbSNP
rs1329633220	886	dbSNP
rs1339891380	893	dbSNP
rs1052251835	897	dbSNP
rs1286459966	904	dbSNP
rs957105328	908	dbSNP
rs1216335005	909	dbSNP
rs750779574	911	dbSNP
rs3208680	914	dbSNP
rs998965064	919	dbSNP
rs1272868134	923	dbSNP
rs1312939254	924	dbSNP
rs1339671718	930	dbSNP
rs903310810	931	dbSNP
rs1197113435	932	dbSNP
rs3208681	933	dbSNP
rs3208682	934	dbSNP
rs3208683	938	dbSNP
rs1043257240	943	dbSNP
rs3208684	947	dbSNP
rs554647826	962	dbSNP
rs947612698	966	dbSNP
rs1185381532	967	dbSNP
rs1244872626	975	dbSNP
rs916206720	979	dbSNP
rs1402079072	982	dbSNP
rs1001422125	984	dbSNP
rs768032844	988	dbSNP
rs1463871491	991	dbSNP
rs542672064	993	dbSNP
rs1168703120	1011	dbSNP
rs1401668119	1014	dbSNP
rs192023484	1017	dbSNP
rs1339323713	1023	dbSNP
rs1384208295	1024	dbSNP
rs937704469	1028	dbSNP
rs1013582422	1030	dbSNP
rs553855036	1039	dbSNP
rs1328507787	1042	dbSNP
rs1476932291	1043	dbSNP
rs1251497143	1052	dbSNP
rs1420185462	1053	dbSNP
rs1343735626	1056	dbSNP
rs1188329969	1057	dbSNP
rs927665237	1058	dbSNP
rs758028362	1062	dbSNP
rs1198256055	1064	dbSNP
rs1264420896	1067	dbSNP
rs1187793841	1071	dbSNP
rs745345322	1073	dbSNP
rs1430075342	1074	dbSNP
rs1194212485	1076	dbSNP
rs982246124	1076	dbSNP
rs1477133801	1077	dbSNP
rs1178715471	1078	dbSNP
rs1406832982	1087	dbSNP
rs950479047	1092	dbSNP
rs1457189941	1093	dbSNP
rs919083667	1102	dbSNP
rs1387647930	1107	dbSNP
rs1383104954	1114	dbSNP
rs1047144314	1115	dbSNP
rs930050069	1116	dbSNP
rs1197438126	1120	dbSNP
rs1221237965	1125	dbSNP
rs1284666450	1127	dbSNP
rs1323614461	1128	dbSNP
rs1458073735	1130	dbSNP
rs537018288	1134	dbSNP
rs963245815	1135	dbSNP
rs1196434090	1136	dbSNP
rs1266357342	1145	dbSNP
rs1431661789	1148	dbSNP
rs1336482604	1151	dbSNP
rs1037564035	1155	dbSNP
rs188120954	1159	dbSNP
rs1472302496	1161	dbSNP
rs1007487936	1171	dbSNP
rs1338141277	1172	dbSNP
rs1454727310	1184	dbSNP
rs1311245855	1187	dbSNP
rs1439613768	1188	dbSNP
rs1393578586	1199	dbSNP
rs1378129250	1210	dbSNP
rs368749245	1217	dbSNP
rs910510174	1220	dbSNP
rs954847298	1225	dbSNP
rs1227216518	1226	dbSNP
rs1304169504	1229	dbSNP
rs1331082592	1240	dbSNP
rs1318688259	1242	dbSNP
rs1030332085	1243	dbSNP
rs1239596198	1246	dbSNP
rs1464323762	1249	dbSNP
rs752115367	1251	dbSNP
rs1163963370	1256	dbSNP
rs1457491030	1267	dbSNP
rs1269843260	1273	dbSNP
rs1482823858	1274	dbSNP
rs1180148264	1277	dbSNP
rs1252678512	1278	dbSNP
rs867739143	1281	dbSNP
rs922902117	1283	dbSNP
rs903304395	1284	dbSNP
rs988311854	1285	dbSNP
rs956504890	1286	dbSNP
rs184805060	1291	dbSNP
rs554667741	1292	dbSNP
rs1295947703	1305	dbSNP
rs1011777629	1308	dbSNP
rs979657125	1314	dbSNP
rs537638536	1319	dbSNP
rs1208829342	1322	dbSNP
rs759097020	1322	dbSNP
rs1056422275	1328	dbSNP
rs938965741	1329	dbSNP
rs1292181067	1332	dbSNP
rs1341730541	1335	dbSNP
rs1202627574	1338	dbSNP
rs906153196	1349	dbSNP
rs1261912657	1357	dbSNP
rs1046098430	1362	dbSNP
rs865787655	1363	dbSNP
rs1241808467	1372	dbSNP
rs1446917838	1373	dbSNP
rs929055673	1379	dbSNP
rs567420266	1388	dbSNP
rs1389864939	1392	dbSNP
rs1309042682	1393	dbSNP
rs753679722	1395	dbSNP
rs1325159273	1404	dbSNP
rs1355842491	1408	dbSNP
rs908701953	1408	dbSNP
rs1462023611	1410	dbSNP
rs549105385	1416	dbSNP
rs973197792	1422	dbSNP
rs1380534907	1423	dbSNP
rs1454446190	1424	dbSNP
rs527346866	1450	dbSNP
rs1364181676	1452	dbSNP
rs898608725	1462	dbSNP
rs1324497112	1464	dbSNP
rs1386366488	1466	dbSNP
rs910403008	1467	dbSNP
rs986411458	1474	dbSNP
rs138866312	1475	dbSNP
rs1030742158	1487	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.