ID	Duplex structure	Position	Score	MFE
1	miRNA 3' ccGUUUU----UGUCGUUAAUGAAAg 5' |||:: |::|: |||||||| Target 5' gaCAAGGTATTATGGTCATTACTTTg 3'	353 - 378	158.00	-10.20
2	miRNA 3' ccGUUUUUGUCGUUAAUGAAAg 5' || :|||| :: ||:|||| Target 5' caCATGAACA-TGTTTGCTTTt 3'	647 - 667	143.00	-7.80
3	miRNA 3' ccGUUU--UUGUCGUUAAUGAAag 5' |||| :| || :|| |||| Target 5' acCAAAGTGAAAG-GATAACTTcc 3'	928 - 950	109.00	-5.70

Mutant ID	Mutant Position	Mutant Source
COSN30476136	3	COSMIC
COSN30519808	11	COSMIC
COSN30106382	14	COSMIC
COSN26969173	26	COSMIC
COSN30501286	35	COSMIC
COSN31554587	42	COSMIC
COSN31492030	68	COSMIC
COSN31660610	84	COSMIC
COSN30511086	89	COSMIC
COSN31547183	179	COSMIC
COSN1087163	231	COSMIC
COSN31583907	235	COSMIC
COSN30162986	236	COSMIC
COSN26647088	648	COSMIC
COSN16199969	688	COSMIC
COSN31544453	751	COSMIC
COSN31483078	812	COSMIC
COSN30391737	976	COSMIC
COSN31480869	998	COSMIC
COSN16390141	1149	COSMIC
COSN26158725	1254	COSMIC
COSN5353051	1414	COSMIC
COSN31490644	1443	COSMIC
COSN31596271	1445	COSMIC

Mutant ID	Mutant Position	Mutant Source
rs760135290	3	dbSNP
rs765798874	7	dbSNP
rs1295029251	10	dbSNP
rs1212849862	11	dbSNP
rs1319460381	12	dbSNP
rs1220980231	14	dbSNP
rs1256761871	21	dbSNP
rs752864875	23	dbSNP
rs1210764952	24	dbSNP
rs375232761	25	dbSNP
rs368445388	26	dbSNP
rs551198154	29	dbSNP
rs1263977438	37	dbSNP
rs199650232	38	dbSNP
rs1040595141	43	dbSNP
rs1169189691	47	dbSNP
rs780975520	48	dbSNP
rs200171825	49	dbSNP
rs1443570098	57	dbSNP
rs1241103544	69	dbSNP
rs1178721782	79	dbSNP
rs1049248507	82	dbSNP
rs1363570114	87	dbSNP
rs1250670969	92	dbSNP
rs1437907362	92	dbSNP
rs371240455	116	dbSNP
rs1361725916	117	dbSNP
rs530446657	118	dbSNP
rs1245540829	124	dbSNP
rs1296686455	126	dbSNP
rs1330863170	130	dbSNP
rs1309695646	131	dbSNP
rs1392305028	134	dbSNP
rs879857260	138	dbSNP
rs185470302	141	dbSNP
rs1022747302	144	dbSNP
rs1366908393	150	dbSNP
rs1257981256	153	dbSNP
rs369766070	156	dbSNP
rs1208127202	157	dbSNP
rs1183784206	160	dbSNP
rs1266322760	161	dbSNP
rs1419478259	165	dbSNP
rs1373080016	171	dbSNP
rs971050480	172	dbSNP
rs189899505	179	dbSNP
rs1490804334	181	dbSNP
rs1269768756	191	dbSNP
rs1221843324	198	dbSNP
rs1357616314	201	dbSNP
rs1262735257	206	dbSNP
rs1239977495	207	dbSNP
rs552801804	212	dbSNP
rs566557789	214	dbSNP
rs538790200	215	dbSNP
rs1266642633	221	dbSNP
rs1188815731	223	dbSNP
rs1204251382	223	dbSNP
rs1387891563	223	dbSNP
rs140993095	223	dbSNP
rs1453938218	223	dbSNP
rs1156673395	227	dbSNP
rs1363027378	227	dbSNP
rs1481417733	229	dbSNP
rs1198533164	230	dbSNP
rs370084665	230	dbSNP
rs1002575883	231	dbSNP
rs1283229776	231	dbSNP
rs1318345157	231	dbSNP
rs1319656222	231	dbSNP
rs1382495213	231	dbSNP
rs1383790004	231	dbSNP
rs1429679233	231	dbSNP
rs1433630786	231	dbSNP
rs1491207719	231	dbSNP
rs58051216	231	dbSNP
rs72984526	231	dbSNP
rs753090322	231	dbSNP
rs1491091948	232	dbSNP
rs1200815442	233	dbSNP
rs1031965417	234	dbSNP
rs199782772	235	dbSNP
rs1271500751	236	dbSNP
rs72984529	236	dbSNP
rs1325545472	237	dbSNP
rs990358474	237	dbSNP
rs1335822493	238	dbSNP
rs1406557026	238	dbSNP
rs1021442891	239	dbSNP
rs1156231187	239	dbSNP
rs1390244517	243	dbSNP
rs1398503035	249	dbSNP
rs1298711396	250	dbSNP
rs1194448446	251	dbSNP
rs371510141	252	dbSNP
rs3103452	253	dbSNP
rs1289932384	254	dbSNP
rs1390731036	255	dbSNP
rs1428338418	256	dbSNP
rs1385445120	259	dbSNP
rs1303882172	261	dbSNP
rs1388359339	273	dbSNP
rs557988674	283	dbSNP
rs574588878	289	dbSNP
rs1445405191	298	dbSNP
rs1242984677	320	dbSNP
rs954037232	331	dbSNP
rs1440099466	333	dbSNP
rs578027981	336	dbSNP
rs1228051821	339	dbSNP
rs1195686530	342	dbSNP
rs1340846143	345	dbSNP
rs543869587	351	dbSNP
rs1247787091	361	dbSNP
rs1331302078	362	dbSNP
rs1283420694	365	dbSNP
rs1445509898	366	dbSNP
rs1216635410	373	dbSNP
rs986176305	382	dbSNP
rs1329461563	385	dbSNP
rs557384181	400	dbSNP
rs1390709091	403	dbSNP
rs1368814543	411	dbSNP
rs1165522915	413	dbSNP
rs1487496962	414	dbSNP
rs193287417	416	dbSNP
rs1161885509	417	dbSNP
rs944674026	424	dbSNP
rs1471366890	425	dbSNP
rs976058931	438	dbSNP
rs1181751090	439	dbSNP
rs759229261	443	dbSNP
rs1482349753	448	dbSNP
rs138470036	450	dbSNP
rs1224068625	458	dbSNP
rs1472037315	462	dbSNP
rs1179595882	464	dbSNP
rs149626944	470	dbSNP
rs1352611639	475	dbSNP
rs929588299	484	dbSNP
rs1279868451	487	dbSNP
rs1060168	495	dbSNP
rs1409186030	500	dbSNP
rs184963414	504	dbSNP
rs541959453	511	dbSNP
rs1405612956	512	dbSNP
rs1349310543	524	dbSNP
rs887936156	529	dbSNP
rs1409241711	533	dbSNP
rs1158324734	539	dbSNP
rs1044163159	542	dbSNP
rs1432067346	547	dbSNP
rs1200709146	552	dbSNP
rs1163531043	563	dbSNP
rs1368342632	566	dbSNP
rs906960608	574	dbSNP
rs1490371791	576	dbSNP
rs1456847129	580	dbSNP
rs1002515311	589	dbSNP
rs1448348298	590	dbSNP
rs767322839	593	dbSNP
rs867900104	602	dbSNP
rs1031347486	610	dbSNP
rs1306370280	643	dbSNP
rs1223968387	648	dbSNP
rs1367030204	655	dbSNP
rs189346901	657	dbSNP
rs755797974	665	dbSNP
rs1320374264	678	dbSNP
rs953871260	682	dbSNP
rs1060171	685	dbSNP
rs985267237	693	dbSNP
rs1177827754	697	dbSNP
rs1480367997	698	dbSNP
rs1423915726	699	dbSNP
rs1188916562	715	dbSNP
rs1312107987	716	dbSNP
rs375436901	723	dbSNP
rs1242322968	727	dbSNP
rs34621455	727	dbSNP
rs564859396	733	dbSNP
rs1246939166	746	dbSNP
rs1264725113	748	dbSNP
rs1292168690	753	dbSNP
rs34392165	753	dbSNP
rs1311506361	756	dbSNP
rs966118942	770	dbSNP
rs1216393128	772	dbSNP
rs1362683161	773	dbSNP
rs180885116	775	dbSNP
rs1297147585	785	dbSNP
rs1433118760	786	dbSNP
rs1385464653	796	dbSNP
rs1202843874	798	dbSNP
rs1253508775	802	dbSNP
rs550206952	809	dbSNP
rs976026331	816	dbSNP
rs919252723	833	dbSNP
rs1390180633	844	dbSNP
rs1187568596	848	dbSNP
rs1480763274	860	dbSNP
rs929324026	868	dbSNP
rs1244791762	870	dbSNP
rs1180705843	881	dbSNP
rs1183970183	882	dbSNP
rs1253504489	884	dbSNP
rs369709648	888	dbSNP
rs1254192332	890	dbSNP
rs144340014	894	dbSNP
rs1802930	896	dbSNP
rs1165998636	897	dbSNP
rs1386456493	899	dbSNP
rs1429502667	905	dbSNP
rs1361820858	908	dbSNP
rs1316252915	909	dbSNP
rs948833792	910	dbSNP
rs753444444	929	dbSNP
rs1300420583	930	dbSNP
rs1443507588	935	dbSNP
rs1802931	942	dbSNP
rs553929612	943	dbSNP
rs1044600524	953	dbSNP
rs1167386234	955	dbSNP
rs752157321	956	dbSNP
rs1386697426	959	dbSNP
rs906921260	969	dbSNP
rs938396842	970	dbSNP
rs756806238	976	dbSNP
rs546504763	981	dbSNP
rs1053301009	987	dbSNP
rs17038587	1004	dbSNP
rs1251226041	1015	dbSNP
rs557368269	1022	dbSNP
rs1454694024	1023	dbSNP
rs1292795306	1033	dbSNP
rs1021506771	1035	dbSNP
rs538482739	1036	dbSNP
rs185144332	1038	dbSNP
rs1309537021	1040	dbSNP
rs1224869398	1043	dbSNP
rs779601831	1045	dbSNP
rs1006655493	1047	dbSNP
rs1019420249	1054	dbSNP
rs1225831367	1076	dbSNP
rs965213355	1082	dbSNP
rs1293785624	1093	dbSNP
rs571692898	1097	dbSNP
rs1457053968	1108	dbSNP
rs997592699	1109	dbSNP
rs373245753	1112	dbSNP
rs746405272	1127	dbSNP
rs1160979035	1129	dbSNP
rs1472915716	1133	dbSNP
rs1411128370	1135	dbSNP
rs1179849332	1141	dbSNP
rs1209018747	1143	dbSNP
rs758921582	1144	dbSNP
rs1253934157	1150	dbSNP
rs1209489013	1168	dbSNP
rs950741912	1170	dbSNP
rs1368508754	1173	dbSNP
rs375996648	1178	dbSNP
rs1216943145	1199	dbSNP
rs1328847260	1202	dbSNP
rs1287009359	1206	dbSNP
rs1060223	1231	dbSNP
rs909425644	1232	dbSNP
rs1346873063	1237	dbSNP
rs865859799	1238	dbSNP
rs1449406359	1241	dbSNP
rs1186989966	1244	dbSNP
rs1301334542	1250	dbSNP
rs781110294	1250	dbSNP
rs1385912008	1251	dbSNP
rs141585194	1255	dbSNP
rs1388128117	1256	dbSNP
rs1422131161	1257	dbSNP
rs190014254	1268	dbSNP
rs780478319	1270	dbSNP
rs1457584093	1274	dbSNP
rs1175599279	1277	dbSNP
rs564446897	1278	dbSNP
rs747267575	1287	dbSNP
rs980377305	1290	dbSNP
rs1198247329	1291	dbSNP
rs377327721	1300	dbSNP
rs1431723398	1307	dbSNP
rs181275772	1308	dbSNP
rs938868225	1312	dbSNP
rs1464754376	1315	dbSNP
rs1337487159	1321	dbSNP
rs1364288644	1323	dbSNP
rs1206177324	1325	dbSNP
rs1346291161	1326	dbSNP
rs1256144793	1330	dbSNP
rs1052865381	1339	dbSNP
rs572578964	1341	dbSNP
rs1238	1344	dbSNP
rs1218472426	1349	dbSNP
rs748304730	1364	dbSNP
rs1325311363	1370	dbSNP
rs11550186	1374	dbSNP
rs11550187	1378	dbSNP
rs889672428	1392	dbSNP
rs1006750125	1393	dbSNP
rs1402810480	1399	dbSNP
rs1171876200	1401	dbSNP
rs1464615976	1409	dbSNP
rs1040964063	1411	dbSNP
rs1374828507	1417	dbSNP
rs1449066334	1417	dbSNP
rs901012482	1417	dbSNP
rs35252221	1419	dbSNP
rs150502755	1433	dbSNP
rs1203677660	1436	dbSNP
rs1266939685	1445	dbSNP
rs1443556337	1446	dbSNP
rs12561953	1449	dbSNP
rs1207412941	1450	dbSNP
rs994444120	1457	dbSNP
rs1276090154	1461	dbSNP
rs1228743102	1464	dbSNP
rs1340979031	1467	dbSNP
rs1244380355	1474	dbSNP
rs1475928107	1476	dbSNP
rs1026366363	1477	dbSNP
rs1191038644	1481	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.

- Nature, 2013

Circular RNAs (circRNAs) in animals are an enigmatic class of RNA with unknown function. To explore circRNAs systematically, we sequenced and computationally analysed human, mouse and nematode RNA. We detected thousands of well-expressed, stable circRNAs, often showing tissue/developmental-stage-specific expression. Sequence analysis indicated important regulatory functions for circRNAs. We found that a human circRNA, antisense to the cerebellar degeneration-related protein 1 transcript (CDR1as), is densely bound by microRNA (miRNA) effector complexes and harbours 63 conserved binding sites for the ancient miRNA miR-7. Further analyses indicated that CDR1as functions to bind miR-7 in neuronal tissues. Human CDR1as expression in zebrafish impaired midbrain development, similar to knocking down miR-7, suggesting that CDR1as is a miRNA antagonist with a miRNA-binding capacity ten times higher than any other known transcript. Together, our data provide evidence that circRNAs form a large class of post-transcriptional regulators. Numerous circRNAs form by head-to-tail splicing of exons, suggesting previously unrecognized regulatory potential of coding sequences.

- Genome biology, 2014

BACKGROUND: Various microRNAs (miRNAs) are up- or downregulated in tumors. However, the repression of cognate miRNA targets responsible for the phenotypic effects of this dysregulation in patients remains largely unexplored. To define miRNA targets and associated pathways, together with their relationship to outcome in breast cancer, we integrated patient-paired miRNA-mRNA expression data with a set of validated miRNA targets and pathway inference. RESULTS: To generate a biochemically-validated set of miRNA-binding sites, we performed argonaute-2 photoactivatable-ribonucleoside-enhanced crosslinking and immunoprecipitation (AGO2-PAR-CLIP) in MCF7 cells. We then defined putative miRNA-target interactions using a computational model, which ranked and selected additional TargetScan-predicted interactions based on features of our AGO2-PAR-CLIP binding-site data. We subselected modeled interactions according to the abundance of their constituent miRNA and mRNA transcripts in tumors, and we took advantage of the variability of miRNA expression within molecular subtypes to detect miRNA repression. Interestingly, our data suggest that miRNA families control subtype-specific pathways; for example, miR-17, miR-19a, miR-25, and miR-200b show high miRNA regulatory activity in the triple-negative, basal-like subtype, whereas miR-22 and miR-24 do so in the HER2 subtype. An independent dataset validated our findings for miR-17 and miR-25, and showed a correlation between the expression levels of miR-182 targets and overall patient survival. Pathway analysis associated miR-17, miR-19a, and miR-200b with leukocyte transendothelial migration. CONCLUSIONS: We combined PAR-CLIP data with patient expression data to predict regulatory miRNAs, revealing potential therapeutic targets and prognostic markers in breast cancer.