>ALYREF|NM_005782|3'UTR
   1 ACAGACCAGCAAATCCGCGTGCGGAACAGGACCCAGGCGTCTCCTCTTGCTCCCTGGTTGGGGGGCGGTGGCTGGGGCTG
  81 TGCGGCCAATGATGGATTTGTTTCTTTTATGTTTTAAAATAGGATTTAAAAACTCATGTAAAGGTTTTTTTTTTTTCTTT
 161 TTTTTTTTTTTTAATTCTGAAACAGACCTGTTTTGTACCGAGTTATTTTTGGGATAAATTTTACTGGTTGCTGTTGTGGA
 241 GAAGGTGGCGTTTCCACCTTTTCCATAATAAAATAGAAATGTGTGTAGAACTGGAAAAAAAAAAAAAAAAAA

ID	Duplex structure	Position	Score	MFE
1	miRNA 3' guUUUCAUUA-ACGGCCAAAAAc 5' ||| | || | ||||||| Target 5' aaAAACTCATGTAAAGGTTTTTt 3'	128 - 150	152.00	-5.70
2	miRNA 3' guUUUCAUUAACGGCCAAaaac 5' ||| | || |:|||| Target 5' atAAATT--TTACTGGTTgctg 3'	214 - 233	100.00	-9.10
3	miRNA 3' guuuucAUUAACGGCCAAaaac 5' |: | |:|||| Target 5' tcctctTGCTCCCTGGTTgggg 3'	42 - 63	88.00	-6.60

Mutant ID	Mutant Position	Mutant Source
COSN31535757	15	COSMIC
COSN30469271	16	COSMIC
COSN26965876	17	COSMIC
COSN30100246	18	COSMIC
COSN5268339	39	COSMIC
COSN30144975	49	COSMIC
COSN30544105	52	COSMIC
COSN30455772	54	COSMIC
COSN30143667	60	COSMIC
COSN5421227	64	COSMIC
COSN31613622	67	COSMIC
COSN30514273	83	COSMIC
COSN31583499	113	COSMIC
COSN19639130	138	COSMIC
COSN31523355	154	COSMIC
COSN30497151	155	COSMIC
COSN24729313	156	COSMIC
COSN17035292	157	COSMIC
COSN28641218	158	COSMIC
COSN31923298	158	COSMIC
COSN26074980	166	COSMIC
COSN31529693	200	COSMIC
COSN26643844	213	COSMIC
COSN31483163	241	COSMIC

Mutant ID	Mutant Position	Mutant Source
rs747578388	2	dbSNP
rs779790027	2	dbSNP
rs550241378	4	dbSNP
rs749899365	6	dbSNP
rs761527548	6	dbSNP
rs764543521	10	dbSNP
rs780801463	10	dbSNP
rs763559518	16	dbSNP
rs765655164	17	dbSNP
rs759827154	18	dbSNP
rs374614336	19	dbSNP
rs754571266	21	dbSNP
rs932599838	21	dbSNP
rs760699373	22	dbSNP
rs773380671	23	dbSNP
rs1355707547	24	dbSNP
rs371360910	28	dbSNP
rs1361589661	29	dbSNP
rs1292847460	33	dbSNP
rs772021827	34	dbSNP
rs145890926	39	dbSNP
rs778991439	42	dbSNP
rs377486921	43	dbSNP
rs1210700313	44	dbSNP
rs1258576577	45	dbSNP
rs1006687270	46	dbSNP
rs1373069281	47	dbSNP
rs749034093	48	dbSNP
rs1384422837	50	dbSNP
rs1484367107	52	dbSNP
rs193202460	53	dbSNP
rs776034522	56	dbSNP
rs374420797	57	dbSNP
rs188689322	60	dbSNP
rs1264759711	61	dbSNP
rs1242600749	63	dbSNP
rs1429248588	64	dbSNP
rs538320932	65	dbSNP
rs1392023381	66	dbSNP
rs149852847	66	dbSNP
rs368637516	66	dbSNP
rs980374743	67	dbSNP
rs1359479928	74	dbSNP
rs1293920152	80	dbSNP
rs907458252	83	dbSNP
rs373834333	84	dbSNP
rs369093482	87	dbSNP
rs1011728766	90	dbSNP
rs946223257	91	dbSNP
rs1281521162	94	dbSNP
rs1392307857	101	dbSNP
rs1390550344	104	dbSNP
rs549542402	107	dbSNP
rs1054224558	110	dbSNP
rs1463422395	111	dbSNP
rs1251161281	114	dbSNP
rs574723667	118	dbSNP
rs935725961	123	dbSNP
rs1425743439	125	dbSNP
rs1471993811	129	dbSNP
rs1156649412	130	dbSNP
rs1344304909	131	dbSNP
rs1457381299	132	dbSNP
rs1321988346	133	dbSNP
rs1368086073	137	dbSNP
rs913648382	138	dbSNP
rs1276012356	139	dbSNP
rs910914455	144	dbSNP
rs1361686041	146	dbSNP
rs1283923206	149	dbSNP
rs1317760702	150	dbSNP
rs1050222640	151	dbSNP
rs1271385788	152	dbSNP
rs1468120550	153	dbSNP
rs1419445900	154	dbSNP
rs1247276078	157	dbSNP
rs1478964173	157	dbSNP
rs879002268	157	dbSNP
rs374325618	158	dbSNP
rs1472726947	159	dbSNP
rs898440451	161	dbSNP
rs1391805188	162	dbSNP
rs1469710434	163	dbSNP
rs1038267687	164	dbSNP
rs939825482	166	dbSNP
rs1208131302	168	dbSNP
rs1327222535	169	dbSNP
rs1279364556	170	dbSNP
rs908388180	170	dbSNP
rs1230584787	172	dbSNP
rs1291713534	172	dbSNP
rs1202294359	173	dbSNP
rs1210578317	173	dbSNP
rs1232121602	173	dbSNP
rs1292031819	173	dbSNP
rs1334422712	173	dbSNP
rs545535430	173	dbSNP
rs1056216028	174	dbSNP
rs1240103416	175	dbSNP
rs958129113	177	dbSNP
rs556404891	178	dbSNP
rs1474639063	179	dbSNP
rs1163350941	184	dbSNP
rs939134449	188	dbSNP
rs185825836	189	dbSNP
rs1320533955	192	dbSNP
rs1328829130	195	dbSNP
rs1371684392	198	dbSNP
rs1311434701	199	dbSNP
rs1245720040	200	dbSNP
rs1355063695	200	dbSNP
rs1286049886	205	dbSNP
rs1337484321	206	dbSNP
rs980870657	224	dbSNP
rs985518603	225	dbSNP
rs1207044442	228	dbSNP
rs1456222766	239	dbSNP
rs1382224182	242	dbSNP
rs955312843	249	dbSNP
rs922515037	251	dbSNP
rs1453941082	253	dbSNP
rs1441511451	256	dbSNP
rs1187768562	258	dbSNP
rs1238816820	264	dbSNP
rs972610995	265	dbSNP
rs1166790488	268	dbSNP
rs1391393101	274	dbSNP
rs914799736	282	dbSNP
rs990407219	283	dbSNP
rs1455439242	290	dbSNP
rs1396858521	291	dbSNP
rs1336445393	292	dbSNP
rs34992198	295	dbSNP
rs759633919	297	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.