ID	Duplex structure	Position	Score	MFE
1	miRNA 3' ccuuucgauccUCCGGCAUAUc 5' || |:||:|: Target 5' gggtgccacccAGCCTGTGTGc 3'	111 - 132	99.00	-9.10
2	miRNA 3' ccuUUCGAUCCUCCGGCAUAuc 5' |: | || :||| ||:| Target 5' tgcAGACAAGTGGGCGGTGTcc 3'	300 - 321	95.00	-9.70
3	miRNA 3' ccUUUC--GA--UCCU---CCGGCAUAUc 5' |:|| || |||: | || |:|: Target 5' ggAGAGGCCTGCAGGGCTCGACCCTGTGg 3'	185 - 213	88.00	-17.90

Mutant ID	Mutant Position	Mutant Source
COSN30476736	2	COSMIC
COSN30523209	15	COSMIC
COSN24305993	22	COSMIC
COSN505936	37	COSMIC
COSN24034315	57	COSMIC
COSN13755347	58	COSMIC
COSN31556418	64	COSMIC
COSN26646699	65	COSMIC
COSN30535429	74	COSMIC
COSN30713175	79	COSMIC
COSN30182247	84	COSMIC
COSN26678630	88	COSMIC
COSN26636534	124	COSMIC
COSN30609352	139	COSMIC
COSN31578828	215	COSMIC
COSN15665798	224	COSMIC
COSN31561884	242	COSMIC
COSN31588918	289	COSMIC
COSN26637839	302	COSMIC

Mutant ID	Mutant Position	Mutant Source
rs1403609218	2	dbSNP
rs773849713	5	dbSNP
rs759173118	10	dbSNP
rs764779002	11	dbSNP
rs1174415373	17	dbSNP
rs1430122459	21	dbSNP
rs1296346105	22	dbSNP
rs752328214	23	dbSNP
rs762622123	25	dbSNP
rs1283088177	26	dbSNP
rs1343305167	27	dbSNP
rs1186481271	28	dbSNP
rs140755185	31	dbSNP
rs751301684	33	dbSNP
rs984435916	34	dbSNP
rs757193775	36	dbSNP
rs369830273	37	dbSNP
rs1264652350	39	dbSNP
rs1488606670	40	dbSNP
rs750349647	41	dbSNP
rs756198329	42	dbSNP
rs760497815	43	dbSNP
rs75363570	44	dbSNP
rs749504466	45	dbSNP
rs1442233984	48	dbSNP
rs57800087	50	dbSNP
rs779148528	51	dbSNP
rs1307900535	55	dbSNP
rs150111604	57	dbSNP
rs138450617	58	dbSNP
rs1356770986	62	dbSNP
rs184414541	64	dbSNP
rs769215319	65	dbSNP
rs1303059561	66	dbSNP
rs775020127	69	dbSNP
rs763739435	70	dbSNP
rs1463819658	71	dbSNP
rs1275766272	73	dbSNP
rs773990493	74	dbSNP
rs12841	83	dbSNP
rs761657065	86	dbSNP
rs767279761	87	dbSNP
rs750401131	90	dbSNP
rs111309938	91	dbSNP
rs766382520	95	dbSNP
rs926203424	96	dbSNP
rs936298385	100	dbSNP
rs753888910	101	dbSNP
rs563848936	102	dbSNP
rs779334656	104	dbSNP
rs946010907	106	dbSNP
rs1157075639	113	dbSNP
rs764051315	114	dbSNP
rs879464806	116	dbSNP
rs1162665697	119	dbSNP
rs1045834282	121	dbSNP
rs1389241489	122	dbSNP
rs758871614	124	dbSNP
rs1324682177	128	dbSNP
rs1335517983	130	dbSNP
rs1179222774	132	dbSNP
rs1444215699	132	dbSNP
rs1310986249	138	dbSNP
rs1250580223	139	dbSNP
rs778239246	139	dbSNP
rs1240186456	146	dbSNP
rs78625180	153	dbSNP
rs771415364	158	dbSNP
rs774871104	159	dbSNP
rs1232142994	161	dbSNP
rs749957833	167	dbSNP
rs1210327320	168	dbSNP
rs1272110564	171	dbSNP
rs1456266762	174	dbSNP
rs1338230321	176	dbSNP
rs947859568	176	dbSNP
rs570009667	177	dbSNP
rs1240264340	179	dbSNP
rs1374430956	182	dbSNP
rs1046582958	185	dbSNP
rs1440507602	187	dbSNP
rs1186955738	188	dbSNP
rs1397324300	189	dbSNP
rs761612913	192	dbSNP
rs765850933	192	dbSNP
rs1459937137	193	dbSNP
rs1164343007	197	dbSNP
rs1400102861	198	dbSNP
rs1366821025	199	dbSNP
rs1464407615	200	dbSNP
rs1033546082	203	dbSNP
rs768040376	204	dbSNP
rs774041060	205	dbSNP
rs1310019746	209	dbSNP
rs1469701064	214	dbSNP
rs1341736883	220	dbSNP
rs1245503778	221	dbSNP
rs761425733	224	dbSNP
rs10013	226	dbSNP
rs1017250004	228	dbSNP
rs1213038380	230	dbSNP
rs961084048	233	dbSNP
rs751103779	237	dbSNP
rs537465571	239	dbSNP
rs1458418579	241	dbSNP
rs994212437	242	dbSNP
rs555445570	243	dbSNP
rs766405936	247	dbSNP
rs1188270419	250	dbSNP
rs1174465064	251	dbSNP
rs955161426	256	dbSNP
rs985175392	263	dbSNP
rs911416337	265	dbSNP
rs1018086001	268	dbSNP
rs1477106444	271	dbSNP
rs1454425486	274	dbSNP
rs919993560	274	dbSNP
rs765351326	275	dbSNP
rs957523289	276	dbSNP
rs990430814	278	dbSNP
rs1447394647	280	dbSNP
rs753704934	281	dbSNP
rs976840976	285	dbSNP
rs1403827817	288	dbSNP
rs755133243	289	dbSNP
rs1449809087	290	dbSNP
rs967372961	291	dbSNP
rs1328845123	292	dbSNP
rs1338360648	300	dbSNP
rs1283411726	302	dbSNP
rs765374367	303	dbSNP
rs1046110129	304	dbSNP
rs752995777	307	dbSNP
rs977456676	308	dbSNP
rs1232889161	313	dbSNP
rs1254500296	315	dbSNP
rs1484322784	316	dbSNP
rs866310333	317	dbSNP
rs563587647	320	dbSNP
rs1320682454	321	dbSNP
rs750469449	322	dbSNP
rs1196432695	323	dbSNP
rs1424861294	329	dbSNP
rs937446842	332	dbSNP
rs1436847487	334	dbSNP
rs1432981403	336	dbSNP
rs1375776952	340	dbSNP
rs117705554	341	dbSNP
rs778300415	342	dbSNP

- Journal of molecular biology, 2011

The COP9 signalosome (CSN) complex controls protein degradation via the ubiquitin (Ub) proteasome system (UPS) in eukaryotes. In mammalian cells, the multimeric CSN is composed of eight subunits (CSN1 - CSN8). It regulates cullin-RING Ub ligases (CRLs), which target essential regulatory proteins for ubiquitination and subsequent degradation. Thereby, the CSN cooperates with the UPS in a variety of essential cellular functions, including DNA repair, cell cycle and differentiation. Although functions of the CSN have been elucidated, mechanisms and regulatory principles of its de novo formation are completely unknown. Here, we show that there is a fundamental mechanism that allows a coordinated expression of all CSN subunits, a prerequisite for CSN assembly. CSN subunit mRNAs are targets of miRNAs of the let-7 family suppressing CSN subunit expression in human cells. Factors that reduce or block let-7 miRNAs induce the coordinated expression of CSN subunits. For instance, over-expression of CSN1 specifically traps let-7a-1 miRNA and elevates CSN subunit levels by two- to fourfold in a coordinated manner. CSN subunit expression is also increased by specific miRNA inhibitors or by interferon (IFN)-mediated induction of STAT1 and c-Myc reducing levels of let-7 miRNAs. Activation of STAT1 by IFNalpha or IFNgamma induces c-Myc, which increases CSN subunit expression via the Lin28B/let-7 regulatory pathway. By contrast, a let-7a-1 mimic reduces CSN subunit expression. Our data show that let-7 miRNAs control the fine-tuning and coordinated expression of subunits for CSN de novo formation, presumably a general regulatory principle for other Zomes complexes as well.