ID	Duplex structure	Position	Score	MFE
1	miRNA 3' gaccccaccccuGUCUCCGAa 5' ::|||||| Target 5' actttccctgtcTGGAGGCTc 3'	34 - 54	125.00	-8.50
2	miRNA 3' gaccccACCCCUG--UCUCCGaa 5' | ||||: :|| || Target 5' gttaatTTGGGATGGGGAAGCaa 3'	135 - 157	85.00	-16.90

Mutant ID	Mutant Position	Mutant Source
COSN30508395	1	COSMIC
COSN26996398	10	COSMIC
COSN5853193	14	COSMIC
COSN30526501	15	COSMIC
COSN31552392	25	COSMIC
COSN26996399	44	COSMIC
COSN30191847	48	COSMIC
COSN30153010	82	COSMIC
COSN31525350	99	COSMIC
COSN31608533	112	COSMIC

Mutant ID	Mutant Position	Mutant Source
rs763737783	3	dbSNP
rs777730624	9	dbSNP
rs771488180	11	dbSNP
rs1344844035	15	dbSNP
rs1280662539	17	dbSNP
rs747636517	26	dbSNP
rs182843656	27	dbSNP
rs755596947	30	dbSNP
rs757383542	31	dbSNP
rs754623686	32	dbSNP
rs375995840	33	dbSNP
rs1346126504	35	dbSNP
rs200486719	35	dbSNP
rs1238225174	36	dbSNP
rs1412270567	40	dbSNP
rs780372451	42	dbSNP
rs1159140378	43	dbSNP
rs1346164399	43	dbSNP
rs202023433	49	dbSNP
rs555116233	54	dbSNP
rs1038282207	56	dbSNP
rs201120477	63	dbSNP
rs751508693	65	dbSNP
rs1290534651	66	dbSNP
rs1489702694	83	dbSNP
rs763870493	84	dbSNP
rs1213265308	88	dbSNP
rs1271482888	106	dbSNP
rs41309110	106	dbSNP
rs1181638953	124	dbSNP
rs752314043	132	dbSNP
rs1471170907	142	dbSNP
rs1159394918	147	dbSNP
rs536702748	149	dbSNP
rs574687244	150	dbSNP
rs1422951657	155	dbSNP
rs1354124003	175	dbSNP
rs114830288	188	dbSNP
rs1390752056	190	dbSNP
rs1326716487	191	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.