ID	Duplex structure	Position	Score	MFE
1	miRNA 3' gaccccaccccuguCUCCGAa 5' |||||| Target 5' acagatttgattgtGAGGCTt 3'	989 - 1009	120.00	-9.80
2	miRNA 3' gaccccaccccuGUCUCCGAa 5' |||||| | Target 5' caagaaacatttCAGAGGGTa 3'	963 - 983	113.00	-8.50
3	miRNA 3' gaccccACCC-CUGUCUCCGaa 5' |||| |:| ||||| Target 5' gcacttTGGGAGGCCGAGGCag 3'	707 - 728	111.00	-16.00

Mutant ID	Mutant Position	Mutant Source
727973	47	ClinVar
COSM7149503	6	COSMIC
COSM7595163	17	COSMIC
COSM9045928	19	COSMIC
COSM7078198	30	COSMIC
COSN31546863	59	COSMIC
COSN31602602	102	COSMIC
COSN26436217	110	COSMIC
COSN30138807	124	COSMIC
COSN30158122	131	COSMIC
COSN31598386	136	COSMIC
COSN30147003	150	COSMIC
rs11855560	983	GWAS

Mutant ID	Mutant Position	Mutant Source
rs755797075	12	dbSNP
rs374679595	14	dbSNP
rs773392887	17	dbSNP
rs367685211	18	dbSNP
rs745659621	20	dbSNP
rs1422816819	26	dbSNP
rs1263727210	30	dbSNP
rs771863099	41	dbSNP
rs202116013	47	dbSNP
rs1391217140	51	dbSNP
rs1484599682	54	dbSNP
rs749317777	57	dbSNP
rs768856622	61	dbSNP
rs1463689649	62	dbSNP
rs1247360415	70	dbSNP
rs1267920287	75	dbSNP
rs776759010	76	dbSNP
rs761886520	83	dbSNP
rs1219596818	86	dbSNP
rs765677449	95	dbSNP
rs1293286114	98	dbSNP
rs201490271	105	dbSNP
rs773721778	106	dbSNP
rs572082069	111	dbSNP
rs1161891228	120	dbSNP
rs955189786	129	dbSNP
rs771253637	131	dbSNP
rs1046964900	138	dbSNP
rs907104171	142	dbSNP
rs938620366	145	dbSNP
rs749149700	147	dbSNP
rs985081443	156	dbSNP
rs1187936037	158	dbSNP
rs1413147014	159	dbSNP
rs774774081	160	dbSNP
rs894100309	161	dbSNP
rs541728912	172	dbSNP
rs1318071857	173	dbSNP
rs564610977	175	dbSNP
rs1271964587	180	dbSNP
rs1157874226	183	dbSNP
rs1232046948	190	dbSNP
rs533603734	195	dbSNP
rs902975040	210	dbSNP
rs1441865216	218	dbSNP
rs1334344269	223	dbSNP
rs550106020	228	dbSNP
rs562615836	240	dbSNP
rs1334782378	248	dbSNP
rs1162830757	249	dbSNP
rs1459829862	254	dbSNP
rs1419866896	261	dbSNP
rs934808683	266	dbSNP
rs1030482825	276	dbSNP
rs1053331059	278	dbSNP
rs1230950356	278	dbSNP
rs1457913592	280	dbSNP
rs1251876014	294	dbSNP
rs1211227307	304	dbSNP
rs1337604504	305	dbSNP
rs1291305664	319	dbSNP
rs1223700465	326	dbSNP
rs1349040955	327	dbSNP
rs954921437	336	dbSNP
rs1241189239	347	dbSNP
rs1290043522	360	dbSNP
rs1323985359	361	dbSNP
rs1008198050	365	dbSNP
rs1017862702	367	dbSNP
rs1443108485	388	dbSNP
rs1324194310	392	dbSNP
rs537451682	392	dbSNP
rs1228018117	410	dbSNP
rs531443679	413	dbSNP
rs1044379404	414	dbSNP
rs963667514	423	dbSNP
rs973437784	426	dbSNP
rs548261898	427	dbSNP
rs183266329	434	dbSNP
rs1005444125	436	dbSNP
rs770612340	446	dbSNP
rs897093236	452	dbSNP
rs1246757821	457	dbSNP
rs1184968593	459	dbSNP
rs1445732716	462	dbSNP
rs950805719	473	dbSNP
rs879036374	477	dbSNP
rs1241252386	481	dbSNP
rs369695117	481	dbSNP
rs1347433257	482	dbSNP
rs1301608202	490	dbSNP
rs55814668	490	dbSNP
rs774443026	496	dbSNP
rs1472437103	504	dbSNP
rs759697080	507	dbSNP
rs1029532225	514	dbSNP
rs749706413	514	dbSNP
rs1343317489	518	dbSNP
rs1299824671	519	dbSNP
rs533753957	521	dbSNP
rs547696537	525	dbSNP
rs928432674	530	dbSNP
rs938541219	536	dbSNP
rs1056078993	537	dbSNP
rs915870463	550	dbSNP
rs1425294949	551	dbSNP
rs12593359	558	dbSNP
rs533914790	559	dbSNP
rs775800573	587	dbSNP
rs146115814	590	dbSNP
rs1217984944	601	dbSNP
rs569462838	603	dbSNP
rs1051537122	607	dbSNP
rs979092042	609	dbSNP
rs1312954199	629	dbSNP
rs1272410744	633	dbSNP
rs890583422	647	dbSNP
rs138965160	649	dbSNP
rs1309698780	654	dbSNP
rs555409580	659	dbSNP
rs1018268297	661	dbSNP
rs1280095084	676	dbSNP
rs963656658	686	dbSNP
rs989353821	694	dbSNP
rs45511893	695	dbSNP
rs549339717	702	dbSNP
rs1305166095	704	dbSNP
rs1467277366	705	dbSNP
rs187525601	711	dbSNP
rs558478364	714	dbSNP
rs1234222201	722	dbSNP
rs1317588545	723	dbSNP
rs950090630	731	dbSNP
rs1425134588	733	dbSNP
rs1044513961	736	dbSNP
rs578181752	737	dbSNP
rs950713111	744	dbSNP
rs192004520	749	dbSNP
rs45527134	750	dbSNP
rs1038411089	763	dbSNP
rs928073933	768	dbSNP
rs7180135	774	dbSNP
rs541980711	779	dbSNP
rs1309384705	782	dbSNP
rs1258753517	787	dbSNP
rs994103976	789	dbSNP
rs1334005181	791	dbSNP
rs1291224672	793	dbSNP
rs1397490336	794	dbSNP
rs991371963	795	dbSNP
rs150778189	800	dbSNP
rs1297310873	819	dbSNP
rs1439544267	822	dbSNP
rs1401896316	823	dbSNP
rs1170728914	825	dbSNP
rs1461399325	827	dbSNP
rs527327381	829	dbSNP
rs1416258428	830	dbSNP
rs1434603325	831	dbSNP
rs764494171	832	dbSNP
rs1424832997	846	dbSNP
rs547065959	850	dbSNP
rs570385293	853	dbSNP
rs924252897	854	dbSNP
rs1238887603	855	dbSNP
rs967812650	856	dbSNP
rs1467978978	867	dbSNP
rs56390641	872	dbSNP
rs757846954	877	dbSNP
rs1051908881	879	dbSNP
rs890248746	886	dbSNP
rs878946975	894	dbSNP
rs1246882013	899	dbSNP
rs1008129983	909	dbSNP
rs1039230319	910	dbSNP
rs765852713	918	dbSNP
rs1170435707	936	dbSNP
rs751276848	937	dbSNP
rs549634475	938	dbSNP
rs1371042314	942	dbSNP
rs1221748537	943	dbSNP
rs1378595003	943	dbSNP
rs995064248	946	dbSNP
rs1026579058	948	dbSNP
rs1429006500	954	dbSNP
rs1331460889	960	dbSNP
rs1439437946	964	dbSNP
rs45549040	969	dbSNP
rs1295865411	972	dbSNP
rs1003586646	973	dbSNP
rs1387574097	975	dbSNP
rs1458835276	981	dbSNP
rs1363612866	982	dbSNP
rs11855560	983	dbSNP
rs45507396	985	dbSNP
rs1381079420	994	dbSNP
rs1193236542	1000	dbSNP
rs45577634	1007	dbSNP
rs1269529413	1012	dbSNP
rs1298383989	1013	dbSNP
rs971543750	1014	dbSNP
rs149380275	1019	dbSNP
rs968537295	1022	dbSNP
rs1203017604	1025	dbSNP
rs144755650	1032	dbSNP
rs924532194	1033	dbSNP
rs1488972625	1042	dbSNP
rs934324371	1052	dbSNP
rs974444838	1053	dbSNP
rs918597825	1055	dbSNP
rs1384798404	1056	dbSNP
rs929858381	1073	dbSNP
rs1051033493	1083	dbSNP
rs1251932697	1084	dbSNP
rs771284289	1093	dbSNP
rs987186430	1105	dbSNP
rs1466772770	1110	dbSNP
rs1173300373	1112	dbSNP
rs1452775346	1115	dbSNP
rs1379477892	1117	dbSNP
rs1199612172	1118	dbSNP
rs577922126	1128	dbSNP
rs1433715522	1136	dbSNP
rs1260878903	1141	dbSNP
rs1191416027	1153	dbSNP
rs1489184259	1155	dbSNP
rs1286447392	1158	dbSNP
rs891070243	1160	dbSNP
rs45585734	1169	dbSNP
rs943156782	1174	dbSNP
rs557671115	1176	dbSNP
rs899301889	1181	dbSNP
rs11852786	1188	dbSNP
rs1325343614	1194	dbSNP
rs1276924815	1195	dbSNP
rs1402373990	1199	dbSNP
rs1048006563	1201	dbSNP
rs1168156288	1202	dbSNP
rs45450497	1207	dbSNP
rs1173239890	1208	dbSNP
rs1461606835	1214	dbSNP
rs1371395829	1216	dbSNP
rs1168512146	1218	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.