>UNC93A|NM_001143947|3'UTR
   1 GAGCAGTGAGGTCCGAGGAGGATGAACTCAGAAAGCACCAGCCAGAGAATTTTCTTAGAAGATGCCTCAGGACATAGAGC
  81 GGCTCCTCATCACCATCTCAGCACAATTTGGCCATTCTGAAGAGATCATGTTATTTCACTCTTCATGTATTTTTTTTCTA
 161 TTCTAACAAATTTTTCGTCCACCATCTTAACAGAGATCAAGTGTATACATGAAGGTATCAGTTCATTTAATTTTAGATGC
 241 AAAAGAAAAAGGTCTAACGTACAATCAGCCAATTAGAATTTGCCTGAAATCATAGACTCACCCTAGTTTTATTGCTGTAG
 321 TTGTTTTTAAGAATTGGAAGCCTGCTTAAAAAATGTAGTTGAGCCCCATAATTTTACAAATGGGCGAACTTTTAAACTTC
 401 TAACTCTACTTGGATCAAAACCTCATACATTTTACAAAGGGGTCCTGACAAGTCAGCTGACTCAACCTCACAGAGTCAGG
 481 GGGTGACAAAGCCAGACTGGGGCTCAGGATTCCTGAAACGTGTGGGGTCTGCGTTTCTAAATAAAGACGGTTATTTAATG
 561 GAAAAAAAAAAAAAAAAAAAAAA

ID	Duplex structure	Position	Score	MFE
1	miRNA 3' aagucgggucggagCGGACGAg 5' ||||||| Target 5' tttaagaattggaaGCCTGCTt 3'	326 - 347	140.00	-12.00
2	miRNA 3' aaGUCGG---GUC-GGAGCGGACgag 5' ||||| :|| :|:||||| Target 5' atCAGCCAATTAGAATTTGCCTGaaa 3'	264 - 289	120.00	-20.62
3	miRNA 3' aagUCGGGUCGGAGCGGACGAg 5' :|:|| | | |:| ||| Target 5' aggGGTCCTGACAAGTCAGCTg 3'	438 - 459	107.00	-10.70

Mutant ID	Mutant Position	Mutant Source
COSN30489136	4	COSMIC
COSN31582142	4	COSMIC
COSN31498140	9	COSMIC
COSN8892434	15	COSMIC
COSN31531272	18	COSMIC
COSN30149425	30	COSMIC
COSN28767005	40	COSMIC
COSN22103533	47	COSMIC
COSN30109448	48	COSMIC
COSN30109440	49	COSMIC
COSN27001241	54	COSMIC
COSN31601336	66	COSMIC
COSN30134049	69	COSMIC
COSN30515117	74	COSMIC
COSN28509760	76	COSMIC
COSN30171704	81	COSMIC
COSN27001243	84	COSMIC
COSN31505204	112	COSMIC
COSN19356242	131	COSMIC
COSN31525973	164	COSMIC
COSN14208736	176	COSMIC
COSN20884673	178	COSMIC
COSN6313475	560	COSMIC

Mutant ID	Mutant Position	Mutant Source
rs1201889479	2	dbSNP
rs1258690069	3	dbSNP
rs781435532	11	dbSNP
rs1183487972	12	dbSNP
rs528728931	14	dbSNP
rs664452	15	dbSNP
rs766667263	15	dbSNP
rs756678900	16	dbSNP
rs780091496	21	dbSNP
rs968974108	22	dbSNP
rs1363362326	24	dbSNP
rs1466729526	28	dbSNP
rs1304857898	36	dbSNP
rs1399752465	39	dbSNP
rs749303981	40	dbSNP
rs768622742	48	dbSNP
rs779155488	50	dbSNP
rs558689248	58	dbSNP
rs1450479371	65	dbSNP
rs577857186	71	dbSNP
rs1392816011	76	dbSNP
rs931716542	77	dbSNP
rs1436049961	78	dbSNP
rs1352370938	82	dbSNP
rs113737602	84	dbSNP
rs1344559610	87	dbSNP
rs1428608661	90	dbSNP
rs1385616842	96	dbSNP
rs1332675615	106	dbSNP
rs1290525968	107	dbSNP
rs545019093	108	dbSNP
rs1395812227	110	dbSNP
rs760673811	118	dbSNP
rs1290877509	120	dbSNP
rs1439874094	121	dbSNP
rs1379802688	125	dbSNP
rs1302964981	127	dbSNP
rs1051944252	130	dbSNP
rs1345908443	131	dbSNP
rs540717037	143	dbSNP
rs442368	145	dbSNP
rs1316383932	147	dbSNP
rs1487740228	150	dbSNP
rs67843022	150	dbSNP
rs28373754	177	dbSNP
rs940332885	178	dbSNP
rs1244635336	185	dbSNP
rs544307840	189	dbSNP
rs1193323432	209	dbSNP
rs1280456206	210	dbSNP
rs186595829	216	dbSNP
rs560920126	221	dbSNP
rs1191391525	222	dbSNP
rs1406659342	224	dbSNP
rs796743740	225	dbSNP
rs1162615552	227	dbSNP
rs371335503	230	dbSNP
rs994731759	239	dbSNP
rs796943787	240	dbSNP
rs1191232169	249	dbSNP
rs1323596305	251	dbSNP
rs796117560	251	dbSNP
rs1477325691	255	dbSNP
rs984126788	256	dbSNP
rs1369072717	257	dbSNP
rs1044837504	259	dbSNP
rs974931576	260	dbSNP
rs1443437830	263	dbSNP
rs549744291	266	dbSNP
rs905039498	267	dbSNP
rs1003410444	271	dbSNP
rs1036179218	273	dbSNP
rs1284204411	283	dbSNP
rs1329471933	292	dbSNP
rs1222091007	302	dbSNP
rs1322942039	307	dbSNP
rs1309795232	311	dbSNP
rs960180884	315	dbSNP
rs1398528666	318	dbSNP
rs564776386	320	dbSNP
rs1213484296	325	dbSNP
rs1010627060	346	dbSNP
rs1464913346	347	dbSNP
rs1020317947	349	dbSNP
rs1429670795	353	dbSNP
rs1201193364	354	dbSNP
rs1476819079	360	dbSNP
rs1470081095	364	dbSNP
rs1245690938	366	dbSNP
rs1181884971	381	dbSNP
rs968921975	386	dbSNP
rs979017131	387	dbSNP
rs1260552225	392	dbSNP
rs1197257023	404	dbSNP
rs922214136	412	dbSNP
rs201539330	417	dbSNP
rs953669228	427	dbSNP
rs987681610	429	dbSNP
rs1221197817	437	dbSNP
rs1343136293	447	dbSNP
rs1274398381	453	dbSNP
rs1443039068	462	dbSNP
rs1468166898	478	dbSNP
rs1329253611	479	dbSNP
rs1445925981	479	dbSNP
rs1178360742	481	dbSNP
rs1412656209	483	dbSNP
rs911616851	485	dbSNP
rs1177962045	488	dbSNP
rs1412456545	498	dbSNP
rs940464392	501	dbSNP
rs1424041152	512	dbSNP
rs1158717047	517	dbSNP
rs1162669660	520	dbSNP
rs1235777094	521	dbSNP
rs1035962960	524	dbSNP
rs920263224	533	dbSNP
rs879039451	534	dbSNP
rs1324474896	546	dbSNP
rs930525436	549	dbSNP
rs1044952313	550	dbSNP
rs387155	560	dbSNP
rs1239419983	561	dbSNP
rs939162124	562	dbSNP
rs1383422760	563	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.