ID	Duplex structure	Position	Score	MFE
1	miRNA 3' gugggggugguggUGCGGGc 5' |:|||| Target 5' ttatttttcaaaaATGCCCa 3'	389 - 408	104.00	-10.30
2	miRNA 3' gugggggugguggUGCGGgc 5' |:||| Target 5' aaactaatgagaaATGCCat 3'	69 - 88	84.00	-6.90
3	miRNA 3' gugggggugguGGUGCGGGc 5' |||| ::| Target 5' gagtttggttcCCACTTTCa 3'	104 - 123	81.00	-11.92

Mutant ID	Mutant Position	Mutant Source
COSN30511422	8	COSMIC
COSN30511420	9	COSMIC
COSN19462192	31	COSMIC
COSN30453398	44	COSMIC
COSN20077742	52	COSMIC
COSN30155073	55	COSMIC
COSN31581171	63	COSMIC
COSN30446987	65	COSMIC
COSN30148604	88	COSMIC
COSN30152275	96	COSMIC
COSN31525488	99	COSMIC
COSN31586002	101	COSMIC
COSN8586000	124	COSMIC
COSN28637255	170	COSMIC
COSN22536184	189	COSMIC
COSN31566841	301	COSMIC
COSN29869481	448	COSMIC
COSN31486611	544	COSMIC
COSN30372258	561	COSMIC

Mutant ID	Mutant Position	Mutant Source
rs1244471639	1	dbSNP
rs140283743	2	dbSNP
rs761558428	2	dbSNP
rs769633524	3	dbSNP
rs771759935	4	dbSNP
rs1057085580	5	dbSNP
rs915794016	6	dbSNP
rs369511087	17	dbSNP
rs1388735950	19	dbSNP
rs772819540	21	dbSNP
rs1214383707	33	dbSNP
rs760279522	36	dbSNP
rs1201953055	39	dbSNP
rs771305776	40	dbSNP
rs1262788038	42	dbSNP
rs1184206376	44	dbSNP
rs776800275	47	dbSNP
rs1465553653	49	dbSNP
rs1469897400	52	dbSNP
rs184472712	57	dbSNP
rs11539999	60	dbSNP
rs948440131	61	dbSNP
rs1410938562	62	dbSNP
rs1176610361	65	dbSNP
rs574353842	66	dbSNP
rs1038271779	76	dbSNP
rs552563704	77	dbSNP
rs1464927060	86	dbSNP
rs1249355630	89	dbSNP
rs1207323884	90	dbSNP
rs1464893413	92	dbSNP
rs117220556	93	dbSNP
rs190222249	94	dbSNP
rs146822999	104	dbSNP
rs750910356	113	dbSNP
rs114323263	116	dbSNP
rs562183763	122	dbSNP
rs943946302	123	dbSNP
rs1318690280	125	dbSNP
rs1039603617	136	dbSNP
rs529792454	149	dbSNP
rs1459665882	154	dbSNP
rs549929126	160	dbSNP
rs899746214	169	dbSNP
rs541410860	172	dbSNP
rs998743266	176	dbSNP
rs563258674	178	dbSNP
rs1467349557	185	dbSNP
rs79108287	188	dbSNP
rs1021865622	189	dbSNP
rs1174840475	191	dbSNP
rs1449715882	194	dbSNP
rs1400976670	197	dbSNP
rs375774394	204	dbSNP
rs998987219	205	dbSNP
rs553660884	225	dbSNP
rs1202736670	226	dbSNP
rs1482442556	230	dbSNP
rs139268880	234	dbSNP
rs1206119686	244	dbSNP
rs758923720	245	dbSNP
rs1344668189	247	dbSNP
rs1295458289	255	dbSNP
rs959665687	256	dbSNP
rs991703439	260	dbSNP
rs1022680670	264	dbSNP
rs1228202883	267	dbSNP
rs1311428484	268	dbSNP
rs1313300369	270	dbSNP
rs747326881	274	dbSNP
rs77653313	281	dbSNP
rs973624841	287	dbSNP
rs1312115495	297	dbSNP
rs966794374	300	dbSNP
rs978208496	301	dbSNP
rs1283427136	304	dbSNP
rs1487879924	307	dbSNP
rs769119076	310	dbSNP
rs1190149977	313	dbSNP
rs542069976	314	dbSNP
rs181364628	315	dbSNP
rs993055421	334	dbSNP
rs752285759	345	dbSNP
rs911901155	348	dbSNP
rs1204749541	350	dbSNP
rs1431478138	351	dbSNP
rs943391649	359	dbSNP
rs948620564	360	dbSNP
rs1039048411	375	dbSNP
rs563660359	377	dbSNP
rs899777644	389	dbSNP
rs1338667485	390	dbSNP
rs947274834	398	dbSNP
rs1042913432	410	dbSNP
rs902987734	416	dbSNP
rs1295	419	dbSNP
rs1446457655	421	dbSNP
rs1157147502	431	dbSNP
rs746970857	433	dbSNP
rs1164560859	436	dbSNP
rs1035362259	437	dbSNP
rs895566343	447	dbSNP
rs1417838276	454	dbSNP
rs1012568442	457	dbSNP
rs1181663674	463	dbSNP
rs1250076895	463	dbSNP
rs1473754001	463	dbSNP
rs900918024	466	dbSNP
rs1269557365	474	dbSNP
rs1208185765	479	dbSNP
rs934189358	486	dbSNP
rs1050327668	490	dbSNP
rs1228932359	492	dbSNP
rs1420738503	498	dbSNP
rs1330875791	499	dbSNP
rs1023039036	506	dbSNP
rs1300412835	507	dbSNP
rs890048016	514	dbSNP
rs1324932062	515	dbSNP
rs1384519167	516	dbSNP
rs780321126	517	dbSNP
rs537135102	519	dbSNP
rs902552656	520	dbSNP
rs1410199616	527	dbSNP
rs564923172	528	dbSNP
rs1478464748	529	dbSNP
rs777586179	539	dbSNP
rs1379536927	540	dbSNP
rs1197058812	557	dbSNP
rs1451038233	563	dbSNP
rs1035131023	564	dbSNP
rs1026492865	569	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.