>MGST3|NM_004528|3'UTR
   1 AGAATTATAGGGGTTTAAAAACTCTCATTCATTTTAAATGACTTACCTTTATTTCCAGTTACATTTTTTTTCTAAATATA
  81 ATAAAAACTTACCTGGCATCAGCCTCATACCTAAAACTCCTGACTCTTACCACTCATTTCCGTTTGAGTCTGTATCTGAA
 161 ATCAGTAGCCTAGTCCTACTAGATGAGAAAGGAGCCACAAGTATTGTGCCCTCTCCTCACCCTTCCAGCAGATGCTTCTG
 241 TAGTATGTGAGGTTGAGAAAAAGTCTGATTGTGGTGATGTAGGTATAGTCATGCCACAGTGATGAAAAATTAAAGAAAAA
 321 TCTTCTAGCTCTCAGGATATGCATTATCACTTGCTACAGATACTCCAAGGCCAAAGGAATGCTTGAGCCTAAAAGTTCAA
 401 GACCAGCCTGGGCAACATAGCAAAACCCCATCTCTACAAAAAAATATACAACAGTTAGCCAGGCATGATGGCACATGTCT
 481 GCAGTCCCAGCTACTTGGGAGGCTAAGGTGGGAGGATCACTTGAGCCCAGGGTGTCAAGGCTGCAGTGAGTTATGATCAC
 561 ACTGCTGCACTCCAGCGTGGGTGACAGAGCAAGACCCTGTCTCAAATAAATAAAAATTAAGTTTCTATTAAAAAAAAAAA
 641 A

ID	Duplex structure	Position	Score	MFE
1	miRNA 3' uacaUCCGGAAAUCUAGUGAa 5' |||: :||||||| Target 5' gctaAGGTGGGAGGATCACTt 3'	502 - 522	145.00	-15.40
2	miRNA 3' uaCAUCCGGAAAU-CUAGUGaa 5' ||: | ||| |||||| Target 5' caGTGAG---TTATGATCACac 3'	544 - 562	128.00	-7.50
3	miRNA 3' uacAUCCGGAAAUCUAGUGAa 5' || || || |||||| Target 5' ggaTATGCATT---ATCACTt 3'	335 - 352	126.00	-5.50

Mutant ID	Mutant Position	Mutant Source
COSN30121608	3	COSMIC
COSN30447533	25	COSMIC
COSN30109797	41	COSMIC
COSN30497089	46	COSMIC
COSN30495855	72	COSMIC
COSN30747811	72	COSMIC
COSN7182309	97	COSMIC
COSN32083113	342	COSMIC
COSN1411201	418	COSMIC

Mutant ID	Mutant Position	Mutant Source
rs1414609614	4	dbSNP
rs766507497	9	dbSNP
rs763840126	13	dbSNP
rs751765754	14	dbSNP
rs1458048046	17	dbSNP
rs1323005378	23	dbSNP
rs1381141854	28	dbSNP
rs552488954	43	dbSNP
rs1285366928	45	dbSNP
rs373059941	47	dbSNP
rs755972776	48	dbSNP
rs8133	59	dbSNP
rs531753887	63	dbSNP
rs888063059	64	dbSNP
rs9333486	64	dbSNP
rs75462110	65	dbSNP
rs10102	73	dbSNP
rs1323308841	75	dbSNP
rs1378429849	76	dbSNP
rs1018644468	77	dbSNP
rs964976951	79	dbSNP
rs1334399552	82	dbSNP
rs1196522785	92	dbSNP
rs1247440863	98	dbSNP
rs1261503884	101	dbSNP
rs1192101861	108	dbSNP
rs187363916	115	dbSNP
rs1027909791	127	dbSNP
rs1251315359	133	dbSNP
rs952277267	134	dbSNP
rs534328458	136	dbSNP
rs9333487	142	dbSNP
rs547905565	143	dbSNP
rs1225178087	155	dbSNP
rs939464325	157	dbSNP
rs570688211	162	dbSNP
rs916615860	167	dbSNP
rs1260101333	171	dbSNP
rs376691545	176	dbSNP
rs948661072	180	dbSNP
rs1044664592	186	dbSNP
rs1198295218	189	dbSNP
rs1248679727	191	dbSNP
rs904445447	193	dbSNP
rs966816804	199	dbSNP
rs1447023498	210	dbSNP
rs765928799	215	dbSNP
rs935803838	221	dbSNP
rs9333488	225	dbSNP
rs1167859618	235	dbSNP
rs1460948901	240	dbSNP
rs1372944288	244	dbSNP
rs1368755934	246	dbSNP
rs576228072	250	dbSNP
rs1435341793	251	dbSNP
rs891531751	252	dbSNP
rs1008679980	253	dbSNP
rs34861431	258	dbSNP
rs535442788	258	dbSNP
rs1458345090	269	dbSNP
rs191699838	281	dbSNP
rs4147611	283	dbSNP
rs1194080505	286	dbSNP
rs1480275049	288	dbSNP
rs912449519	299	dbSNP
rs781671733	313	dbSNP
rs1297321721	316	dbSNP
rs1302389248	330	dbSNP
rs1393863601	331	dbSNP
rs943708640	332	dbSNP
rs184727128	336	dbSNP
rs1335280604	354	dbSNP
rs1390258800	357	dbSNP
rs1402282625	360	dbSNP
rs1303970244	367	dbSNP
rs189225437	377	dbSNP
rs1355168268	383	dbSNP
rs1393680091	383	dbSNP
rs9333489	397	dbSNP
rs931070350	398	dbSNP
rs952351433	409	dbSNP
rs140040297	411	dbSNP
rs1004991551	419	dbSNP
rs563202034	422	dbSNP
rs1418647343	429	dbSNP
rs1256917226	438	dbSNP
rs1202155780	445	dbSNP
rs531867339	447	dbSNP
rs1484623353	448	dbSNP
rs1279383101	455	dbSNP
rs1318777716	459	dbSNP
rs1226764130	462	dbSNP
rs1355428362	473	dbSNP
rs1277473764	475	dbSNP
rs1237876274	476	dbSNP
rs1015076462	477	dbSNP
rs1314178777	480	dbSNP
rs1249627823	482	dbSNP
rs1484360420	500	dbSNP
rs960772195	527	dbSNP
rs777910919	528	dbSNP
rs542496705	529	dbSNP
rs916670649	531	dbSNP
rs561985305	532	dbSNP
rs9333490	533	dbSNP
rs1157089363	541	dbSNP
rs547945580	544	dbSNP
rs1469799084	545	dbSNP
rs1369151966	547	dbSNP
rs1185769310	548	dbSNP
rs9333491	549	dbSNP
rs1014044197	551	dbSNP
rs1425687873	555	dbSNP
rs1194286541	556	dbSNP
rs925839279	563	dbSNP
rs1489189081	577	dbSNP
rs935956576	578	dbSNP
rs570922492	586	dbSNP
rs1356560076	595	dbSNP
rs1370777791	599	dbSNP
rs1266701000	608	dbSNP
rs902627211	612	dbSNP
rs1354253543	614	dbSNP
rs1052925339	621	dbSNP
rs576637041	624	dbSNP
rs1401111032	628	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.