ID	Duplex structure	Position	Score	MFE
1	miRNA 3' ucgUCCUCCC--GACC-CGUCCGc 5' ||| ||| |||| |||||| Target 5' tggAGGTGGGGCCTGGAGCAGGCc 3'	1013 - 1036	140.00	-26.80
2	miRNA 3' ucguccucccgaccCGUCCGc 5' |||||| Target 5' acactgacacctttGCAGGCa 3'	79 - 99	120.00	-10.30
3	miRNA 3' ucguccucccgaccCGUCCGc 5' |||||| Target 5' gagcctctgtcactGCAGGCa 3'	258 - 278	120.00	-10.50

Mutant ID	Mutant Position	Mutant Source
COSN30106099	28	COSMIC
COSN9222642	91	COSMIC
COSN30134485	97	COSMIC
COSN20113943	130	COSMIC
COSN23393595	132	COSMIC
COSN30171404	151	COSMIC
COSN16303987	545	COSMIC
COSN5416691	549	COSMIC
COSN9669227	579	COSMIC
COSN6104121	738	COSMIC
COSN1719540	752	COSMIC
COSN6548401	939	COSMIC
COSN30538503	1143	COSMIC
COSN31480706	1174	COSMIC
COSN23830214	1192	COSMIC
COSN24981754	1231	COSMIC
COSN24982495	1233	COSMIC

Mutant ID	Mutant Position	Mutant Source
rs1333460876	8	dbSNP
rs1303345559	10	dbSNP
rs775604728	12	dbSNP
rs749309701	16	dbSNP
rs538898150	17	dbSNP
rs1323710039	18	dbSNP
rs1169899729	19	dbSNP
rs1246038262	27	dbSNP
rs762262550	32	dbSNP
rs1441455861	33	dbSNP
rs772505608	34	dbSNP
rs951259321	35	dbSNP
rs766958331	36	dbSNP
rs1159235132	37	dbSNP
rs777063940	40	dbSNP
rs773000903	49	dbSNP
rs1174947398	50	dbSNP
rs1257880578	52	dbSNP
rs554089116	53	dbSNP
rs1340472263	54	dbSNP
rs1258932347	56	dbSNP
rs1446446695	63	dbSNP
rs1483186583	67	dbSNP
rs1013254730	72	dbSNP
rs1207308761	72	dbSNP
rs1024676814	78	dbSNP
rs917897949	87	dbSNP
rs969143694	88	dbSNP
rs948030049	89	dbSNP
rs1309334046	110	dbSNP
rs1429818353	110	dbSNP
rs143605021	110	dbSNP
rs3833144	110	dbSNP
rs772130515	110	dbSNP
rs879223491	110	dbSNP
rs980390614	110	dbSNP
rs1218367158	114	dbSNP
rs1369622222	114	dbSNP
rs1045309789	125	dbSNP
rs1474651830	129	dbSNP
rs777633125	130	dbSNP
rs1135670	139	dbSNP
rs904076161	143	dbSNP
rs181352385	150	dbSNP
rs747625509	151	dbSNP
rs1188619731	157	dbSNP
rs1423755576	159	dbSNP
rs1255940348	173	dbSNP
rs1184522803	186	dbSNP
rs958506399	193	dbSNP
rs988422010	196	dbSNP
rs1277276783	200	dbSNP
rs1440676025	212	dbSNP
rs1218658748	217	dbSNP
rs1265839707	220	dbSNP
rs1263761654	223	dbSNP
rs1477385441	226	dbSNP
rs1338635300	227	dbSNP
rs1053027549	228	dbSNP
rs1371559376	229	dbSNP
rs891584778	231	dbSNP
rs540625378	232	dbSNP
rs562063359	235	dbSNP
rs1406759992	248	dbSNP
rs1173294181	250	dbSNP
rs574037720	255	dbSNP
rs1164202223	257	dbSNP
rs898270356	258	dbSNP
rs1416415935	259	dbSNP
rs1433445650	265	dbSNP
rs933480101	270	dbSNP
rs890798048	273	dbSNP
rs1251218728	290	dbSNP
rs1179695010	296	dbSNP
rs140241394	301	dbSNP
rs3198502	308	dbSNP
rs533340922	309	dbSNP
rs1332381842	311	dbSNP
rs943463812	317	dbSNP
rs1228959003	320	dbSNP
rs1328328369	325	dbSNP
rs771678248	326	dbSNP
rs1277279180	327	dbSNP
rs1437902563	334	dbSNP
rs962585761	337	dbSNP
rs1331393919	338	dbSNP
rs1322460697	348	dbSNP
rs1386615347	353	dbSNP
rs995373734	354	dbSNP
rs1038089562	359	dbSNP
rs899184171	360	dbSNP
rs183951270	368	dbSNP
rs951524314	369	dbSNP
rs887063959	372	dbSNP
rs188976840	373	dbSNP
rs115942147	374	dbSNP
rs1286667303	381	dbSNP
rs904932829	393	dbSNP
rs969365148	396	dbSNP
rs980706521	397	dbSNP
rs116288652	405	dbSNP
rs936924468	406	dbSNP
rs957733212	410	dbSNP
rs1220512987	415	dbSNP
rs181374973	418	dbSNP
rs1273920511	419	dbSNP
rs1453591078	419	dbSNP
rs1322987724	420	dbSNP
rs1436191314	420	dbSNP
rs187568556	420	dbSNP
rs56975429	420	dbSNP
rs1199813417	422	dbSNP
rs374882566	424	dbSNP
rs772616383	424	dbSNP
rs571349157	426	dbSNP
rs1425997457	428	dbSNP
rs1172018204	432	dbSNP
rs1452821413	432	dbSNP
rs910749041	436	dbSNP
rs1189050270	440	dbSNP
rs1448629034	440	dbSNP
rs943411415	440	dbSNP
rs80291237	442	dbSNP
rs78837207	446	dbSNP
rs1452688878	447	dbSNP
rs1160474848	448	dbSNP
rs1442894623	450	dbSNP
rs1277329664	452	dbSNP
rs1381483231	452	dbSNP
rs973526909	456	dbSNP
rs1297877571	457	dbSNP
rs920558330	464	dbSNP
rs1051306184	465	dbSNP
rs890839241	469	dbSNP
rs1419625266	473	dbSNP
rs1361656700	480	dbSNP
rs1268743171	490	dbSNP
rs1006568299	496	dbSNP
rs115456777	507	dbSNP
rs1393283077	508	dbSNP
rs377109752	509	dbSNP
rs1372701804	517	dbSNP
rs887013108	521	dbSNP
rs949326328	528	dbSNP
rs1417170408	535	dbSNP
rs898454082	543	dbSNP
rs554052709	545	dbSNP
rs1185254188	547	dbSNP
rs905045899	552	dbSNP
rs1025530932	563	dbSNP
rs1002325486	570	dbSNP
rs1448356971	571	dbSNP
rs951309830	576	dbSNP
rs1271338174	578	dbSNP
rs1230320581	582	dbSNP
rs1380611244	583	dbSNP
rs546581419	585	dbSNP
rs1413064330	598	dbSNP
rs145320932	599	dbSNP
rs1308673823	600	dbSNP
rs1013382955	604	dbSNP
rs1025490201	605	dbSNP
rs1352923238	606	dbSNP
rs893588382	607	dbSNP
rs1352973709	608	dbSNP
rs113443901	617	dbSNP
rs536557727	618	dbSNP
rs1180751921	635	dbSNP
rs1251929758	635	dbSNP
rs1356824013	636	dbSNP
rs766189141	637	dbSNP
rs925271276	638	dbSNP
rs958309757	640	dbSNP
rs1322673546	641	dbSNP
rs555761237	643	dbSNP
rs988809525	644	dbSNP
rs1331779226	646	dbSNP
rs1017758539	647	dbSNP
rs1390830224	648	dbSNP
rs1439661803	650	dbSNP
rs1295495535	654	dbSNP
rs1436996102	671	dbSNP
rs1393492207	675	dbSNP
rs573972370	683	dbSNP
rs1157589100	684	dbSNP
rs964882906	699	dbSNP
rs1370651293	705	dbSNP
rs914133116	712	dbSNP
rs920682305	716	dbSNP
rs1391917569	721	dbSNP
rs1057935	724	dbSNP
rs1191381575	725	dbSNP
rs1487931978	736	dbSNP
rs776217451	738	dbSNP
rs1212151382	739	dbSNP
rs1466850155	740	dbSNP
rs987622500	743	dbSNP
rs1269319294	746	dbSNP
rs1315184623	749	dbSNP
rs983451717	749	dbSNP
rs1303735737	757	dbSNP
rs1220053420	763	dbSNP
rs1370446952	764	dbSNP
rs1323647164	765	dbSNP
rs1331500837	768	dbSNP
rs1389360212	769	dbSNP
rs1375481945	770	dbSNP
rs1451045437	775	dbSNP
rs917265742	776	dbSNP
rs73983709	782	dbSNP
rs1046305002	783	dbSNP
rs904993468	788	dbSNP
rs769143524	795	dbSNP
rs937854686	796	dbSNP
rs1340935112	800	dbSNP
rs1257843475	801	dbSNP
rs942423840	807	dbSNP
rs1039416779	811	dbSNP
rs1054064509	817	dbSNP
rs1347512470	822	dbSNP
rs1243806761	823	dbSNP
rs1263456080	831	dbSNP
rs1333042751	850	dbSNP
rs562826364	852	dbSNP
rs1200723615	859	dbSNP
rs1294535553	861	dbSNP
rs898177520	865	dbSNP
rs893546274	866	dbSNP
rs1380481483	869	dbSNP
rs930972272	870	dbSNP
rs578078183	871	dbSNP
rs1433558994	881	dbSNP
rs1373303806	883	dbSNP
rs1042054590	884	dbSNP
rs1047425906	887	dbSNP
rs890140523	892	dbSNP
rs1457384509	904	dbSNP
rs1427258563	910	dbSNP
rs1009120579	912	dbSNP
rs886997622	919	dbSNP
rs1175496754	933	dbSNP
rs537540280	945	dbSNP
rs1017873051	949	dbSNP
rs1278506779	950	dbSNP
rs1024763145	954	dbSNP
rs1340262161	961	dbSNP
rs965372102	962	dbSNP
rs1224885389	970	dbSNP
rs556315173	971	dbSNP
rs1313332955	976	dbSNP
rs117202666	985	dbSNP
rs1352992163	993	dbSNP
rs1416117305	1000	dbSNP
rs1309279065	1001	dbSNP
rs1410064630	1005	dbSNP
rs1028261868	1026	dbSNP
rs560317850	1029	dbSNP
rs527940414	1032	dbSNP
rs983954912	1036	dbSNP
rs1166244908	1041	dbSNP
rs1370750215	1041	dbSNP
rs549283356	1042	dbSNP
rs137952621	1045	dbSNP
rs1304014411	1047	dbSNP
rs1438614777	1049	dbSNP
rs764347941	1050	dbSNP
rs988118264	1052	dbSNP
rs1358176504	1054	dbSNP
rs371020166	1070	dbSNP
rs954975482	1075	dbSNP
rs751791627	1085	dbSNP
rs937956461	1086	dbSNP
rs1228464321	1087	dbSNP
rs1291250786	1091	dbSNP
rs1326416406	1100	dbSNP
rs1390066581	1101	dbSNP
rs1342173959	1104	dbSNP
rs1393367005	1104	dbSNP
rs988084241	1109	dbSNP
rs1218959185	1111	dbSNP
rs910704930	1114	dbSNP
rs1489650683	1115	dbSNP
rs1416245438	1116	dbSNP
rs1161548455	1120	dbSNP
rs757355676	1121	dbSNP
rs1053610708	1123	dbSNP
rs1179888409	1126	dbSNP
rs915080507	1127	dbSNP
rs1253423592	1129	dbSNP
rs781630618	1130	dbSNP
rs1042168491	1150	dbSNP
rs1307068162	1153	dbSNP
rs1205253658	1157	dbSNP
rs1202603599	1159	dbSNP
rs1277223113	1162	dbSNP
rs1234987225	1180	dbSNP
rs1371201838	1184	dbSNP
rs374043277	1200	dbSNP
rs1440625137	1201	dbSNP
rs1392991395	1202	dbSNP
rs975179055	1202	dbSNP
rs1257818183	1203	dbSNP
rs1384392877	1212	dbSNP
rs1156845850	1213	dbSNP
rs1483892121	1216	dbSNP
rs1200354916	1217	dbSNP
rs111430874	1231	dbSNP
rs1008565603	1238	dbSNP
rs1038747297	1248	dbSNP
rs549785396	1252	dbSNP
rs1249861494	1253	dbSNP
rs1216446585	1259	dbSNP
rs1446304592	1261	dbSNP
rs776587800	1261	dbSNP
rs765299038	1262	dbSNP
rs900733832	1262	dbSNP

- Genes & development, 2013

When adapting to environmental stress, cells attenuate and reprogram their translational output. In part, these altered translation profiles are established through changes in the interactions between RNA-binding proteins and mRNAs. The Argonaute 2 (Ago2)/microRNA (miRNA) machinery has been shown to participate in stress-induced translational up-regulation of a particular mRNA, CAT-1; however, a detailed, transcriptome-wide understanding of the involvement of Ago2 in the process has been lacking. Here, we profiled the overall changes in Ago2-mRNA interactions upon arsenite stress by cross-linking immunoprecipitation (CLIP) followed by high-throughput sequencing (CLIP-seq). Ago2 displayed a significant remodeling of its transcript occupancy, with the majority of 3' untranslated region (UTR) and coding sequence (CDS) sites exhibiting stronger interaction. Interestingly, target sites that were destined for release from Ago2 upon stress were depleted in miRNA complementarity signatures, suggesting an alternative mode of interaction. To compare the changes in Ago2-binding patterns across transcripts with changes in their translational states, we measured mRNA profiles on ribosome/polysome gradients by RNA sequencing (RNA-seq). Increased Ago2 occupancy correlated with stronger repression of translation for those mRNAs, as evidenced by a shift toward lighter gradient fractions upon stress, while release of Ago2 was associated with the limited number of transcripts that remained translated. Taken together, these data point to a role for Ago2 and the mammalian miRNAs in mediating the translational component of the stress response.

- 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.