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Dicer

 
Known also as: HERNA, KIAA0928

FUNCTION:

Required for formation of the RNA induced silencing complex (RISC). Component of the RISC loading complex (RLC), also known as the micro-RNA (miRNA) loading complex (miRLC), which is composed of DICER1, EIF2C2/AGO2 and TARBP2. Within the RLC/miRLC, DICER1 and TARBP2 are required to process precursor miRNAs (pre-miRNAs) to mature miRNAs and then load them onto EIF2C2/AGO2. EIF2C2/AGO2 bound to the mature miRNA constitutes the minimal RISC and may subsequently dissociate from DICER1 and TARBP2. Also cleaves double-stranded RNA to produce short interfering RNAs (siRNAs) which target the selective destruction of complementary RNAs.

COFACTOR:

Binds 2 magnesium or manganese ions per subunit (Probable).

SUBUNIT STRUCTURE:

Component of the RISC loading complex (RLC), or micro-RNA (miRNA) loading complex (miRLC), which is composed of DICER1, EIF2C2/AGO2 and TARBP2. Note that the trimeric RLC/miRLC is also referred to as RISC. Interacts with DHX9, EIF2C1, PIWIL1 and PRKRA. Associates with the 60S ribosome.

CELLULAR LOCALIZATION:

Cytoplasm

INVOLVEMENT IN DISEASE:

Defects in DICER1 are a cause of pleuropulmonary blastoma (PPB) [MIM:601200]. PPB is a rare pediatric tumor of the lung that arises during fetal lung development and is often part of an inherited cancer syndrome. PPBs contain both epithelial and mesenchymal cells. Early in tumorigenesis, cysts form in lung airspaces, and these cysts are lined with benign-appearing epithelium. Mesenchymal cells susceptible to malignant transformation reside within the cyst walls and form a dense 'cambium' layer beneath the epithelial lining. In a subset of patients, overgrowth of the mesenchymal cells produces a sarcoma, a transition that is associated with a poorer prognosis.

Defects in DICER1 are the cause of goiter multinodular type 1 with or without Sertoli-Leydig cell tumors (MNG1) [MIM:138800]. A common disorder characterized by nodular overgrowth of the thyroid gland. Some individuals may also develop Sertoli-Leydig cell tumors, usually of the ovary.

Note: DICER1 mutations have been found in uterine cervix embryonal rhabdomyosarcoma, primitive neuroectodermal tumor, Wilms tumor, pulmonary sequestration and juvenile intestinal polyp.




Activities in which Dicer is involved: Pathways in which Dicer is involved:

NCBI GI number(s): 29294649
168693431
29294651
168693430
Species: Homo sapiens

Links to other databases:

Database ID Link
Uniprot Q9UPY3 Q9UPY3
BRENDA - -
KEGG hsa:23405 hsa:23405
PFAM: - Q9UPY3 (Link - using uniprot id)
InterPro: - Q9UPY3 (Link - using uniprot id)
CATH: - -
SCOP: - -
Solved crystal structures: 2EB1
[PDB] [details]


Protein sequence:
MKSPALQPLSMAGLQLMTPASSPMGPFFGLPWQQEAIHDNIYTPRKYQVE
LLEAALDHNTIVCLNTGSGKTFIAVLLTKELSYQIRGDFSRNGKRTVFLV
NSANQVAQQVSAVRTHSDLKVGEYSNLEVNASWTKERWNQEFTKHQVLIM
TCYVALNVLKNGYLSLSDINLLVFDECHLAILDHPYREIMKLCENCPSCP
RILGLTASILNGKCDPEELEEKIQKLEKILKSNAETATDLVVLDRYTSQP
CEIVVDCGPFTDRSGLYERLLMELEEALNFINDCNISVHSKERDSTLISK
QILSDCRAVLVVLGPWCADKVAGMMVRELQKYIKHEQEELHRKFLLFTDT
FLRKIHALCEEHFSPASLDLKFVTPKVIKLLEILRKYKPYERQQFESVEW
YNNRNQDNYVSWSDSEDDDEDEEIEEKEKPETNFPSPFTNILCGIIFVER
RYTAVVLNRLIKEAGKQDPELAYISSNFITGHGIGKNQPRNKQMEAEFRK
QEEVLRKFRAHETNLLIATSIVEEGVDIPKCNLVVRFDLPTEYRSYVQSK
GRARAPISNYIMLADTDKIKSFEEDLKTYKAIEKILRNKCSKSVDTGETD
IDPVMDDDDVFPPYVLRPDDGGPRVTINTAIGHINRYCARLPSDPFTHLA
PKCRTRELPDGTFYSTLYLPINSPLRASIVGPPMSCVRLAERVVALICCE
KLHKIGELDDHLMPVGKETVKYEEELDLHDEEETSVPGRPGSTKRRQCYP
KAIPECLRDSYPRPDQPCYLYVIGMVLTTPLPDELNFRRRKLYPPEDTTR
CFGILTAKPIPQIPHFPVYTRSGEVTISIELKKSGFMLSLQMLELITRLH
QYIFSHILRLEKPALEFKPTDADSAYCVLPLNVVNDSSTLDIDFKFMEDI
EKSEARIGIPSTKYTKETPFVFKLEDYQDAVIIPRYRNFDQPHRFYVADV
YTDLTPLSKFPSPEYETFAEYYKTKYNLDLTNLNQPLLDVDHTSSRLNLL
TPRHLNQKGKALPLSSAEKRKAKWESLQNKQILVPELCAIHPIPASLWRK
AVCLPSILYRLHCLLTAEELRAQTASDAGVGVRSLPADFRYPNLDFGWKK
SIDSKSFISISNSSSAENDNYCKHSTIVPENAAHQGANRTSSLENHDQMS
VNCRTLLSESPGKLHVEVSADLTAINGLSYNQNLANGSYDLANRDFCQGN
QLNYYKQEIPVQPTTSYSIQNLYSYENQPQPSDECTLLSNKYLDGNANKS
TSDGSPVMAVMPGTTDTIQVLKGRMDSEQSPSIGYSSRTLGPNPGLILQA
LTLSNASDGFNLERLEMLGDSFLKHAITTYLFCTYPDAHEGRLSYMRSKK
VSNCNLYRLGKKKGLPSRMVVSIFDPPVNWLPPGYVVNQDKSNTDKWEKD
EMTKDCMLANGKLDEDYEEEDEEEESLMWRAPKEEADYEDDFLEYDQEHI
RFIDNMLMGSGAFVKKISLSPFSTTDSAYEWKMPKKSSLGSMPFSSDFED
FDYSSWDAMCYLDPSKAVEEDDFVVGFWNPSEENCGVDTGKQSISYDLHT
EQCIADKSIADCVEALLGCYLTSCGERAAQLFLCSLGLKVLPVIKRTDRE
KALCPTRENFNSQQKNLSVSCAAASVASSRSSVLKDSEYGCLKIPPRCMF
DHPDADKTLNHLISGFENFEKKINYRFKNKAYLLQAFTHASYHYNTITDC
YQRLEFLGDAILDYLITKHLYEDPRQHSPGVLTDLRSALVNNTIFASLAV
KYDYHKYFKAVSPELFHVIDDFVQFQLEKNEMQGMDSELRRSEEDEEKEE
DIEVPKAMGDIFESLAGAIYMDSGMSLETVWQVYYPMMRPLIEKFSANVP
RSPVRELLEMEPETAKFSPAERTYDGKVRVTVEVVGKGKFKGVGRSYRIA
KSAAARRALRSLKANQPQVPNS

Dicer (Homo sapiens) is product of expression of Dicer gene.

References:

Title Authors Journal Publication date (Issue) PubMed ID
Single processing center models for human Dicer and bacterial RNase III. Zhang H, Kolb FA, Jaskiewicz L, Westhof E, Filipowicz W Cell 2004-07-09 (118) 15242644
Human Dicer preferentially cleaves dsRNAs at their termini without a requirement for ATP. Zhang H, Kolb FA, Brondani V, Billy E, Filipowicz W EMBO J 2002-11-01 (21) 12411505
Homodimeric structure and double-stranded RNA cleavage activity of the C-terminal RNase III domain of human dicer. Takeshita D, Zenno S, Lee WC, Nagata K, Saigo K, Tanokura M J Mol Biol 2007-11-16 (374) 17920623
Autoinhibition of human dicer by its internal helicase domain. Ma E, MacRae IJ, Kirsch JF, Doudna JA J Mol Biol 2008-06-27 (380) 18508075
Crystallization and preliminary X-ray analysis of the C-terminal RNase III domain of human Dicer. Takeshita D, Zenno S, Lee WC, Nagata K, Saigo K, Tanokura M Acta Crystallogr Sect F Struct 2006-04-01 (62) 16582496
Human dicer: purification, properties, and interaction with PAZ PIWI domain proteins. Kolb FA, Zhang H, Jaronczyk K, Tahbaz N, Hobman TC, Filipowicz W Methods Enzymol 2005-01-01 (392) 15644190
The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Gerhard DS, Wagner L, Feingold EA, Shenmen CM, Grouse LH, Schuler G, Klein SL, Old S, Rasooly R, Good P, Guyer M, Peck AM, Derge JG, Lipman D, Collins FS, Jang W, Sherry S, Feolo M, Misquitta L, Lee E, Rotmistrovsky K, Greenhut SF, Schaefer CF, Buetow K, Bonner TI, Haussler D, Kent J, Kiekhaus M, Furey T, Brent M, Prange C, Schreiber K, Shapiro N, Bhat NK, Hopkins RF, Hsie F, Driscoll T, Soares MB, Casavant TL, Scheetz TE, Brown-stein MJ, Usdin TB, Toshiyuki S, Carninci P, Piao Y, Dudekula DB, K Genome Res 2004-10-01 (14) 15489334
TRBP recruits the Dicer complex to Ago2 for microRNA processing and gene silencing. Chendrimada TP, Gregory RI, Kumaraswamy E, Norman J, Cooch N, Nishikura K, Shiekhattar R Nature 2005-08-04 (436) 15973356
Initial characterization of the human central proteome. Burkard TR, Planyavsky M, Kaupe I, Breitwieser FP, Burckstummer T, Bennett KL, Superti-Furga G, Colinge J BMC Syst Biol 2011-01-01 (5) 21269460
A quantitative atlas of mitotic phosphorylation. Dephoure N, Zhou C, Villen J, Beausoleil SA, Bakalarski CE, Elledge SJ, Gygi SP Proc Natl Acad Sci U S A 2008-08-05 (105) 18669648
Construction of expression-ready cDNA clones for KIAA genes: manual curation of 330 KIAA cDNA clones. Nakajima D, Okazaki N, Yamakawa H, Kikuno R, Ohara O, Nagase T DNA Res 2002-06-01 (9) 12168954
Immunoaffinity profiling of tyrosine phosphorylation in cancer cells. Rush J, Moritz A, Lee KA, Guo A, Goss VL, Spek EJ, Zhang H, Zha XM, Polakiewicz RD, Comb MJ Nat Biotechnol 2005-02-01 (23) 15592455
The DNA sequence and analysis of human chromosome 14. Heilig R, Eckenberg R, Petit JL, Fonknechten N, Da Silva C, Cattolico L, Levy M, Barbe V, de Berardinis V, Ureta-Vidal A Nature 2003-01-06 (421) 12508121
Prediction of the coding sequences of unidentified human genes. XIII. The complete sequences of 100 new cDNA clones from brain which code for large proteins in vitro. Nagase T, Ishikawa K, Suyama M, Kikuno R, Hirosawa M, Miyajima N, Tanaka A, Kotani H, Nomura N, Ohara O DNA Res 1999-01-26 (6) 10231032
Molecular cloning and characterization of a novel human gene (HERNA) which encodes a putative RNA-helicase. Matsuda S, Ichigotani Y, Okuda T, Irimura T, Nakatsugawa S, Hamaguchi M Biochim Biophys Acta 2000-02-01 (1490) 10786632
A novel splice variant of the human dicer gene is expressed in neuroblastoma cells. Potenza N, Papa U, Scaruffi P, Mosca N, Tonini GP, Russo A FEBS Lett 2010-08-04 (584) 20615407
Interaction of 5-lipoxygenase with cellular proteins. Provost P, Samuelsson B, Radmark O Proc Natl Acad Sci U S A 1999-03-02 (96) 10051563
Characterization of the interactions between mammalian PAZ PIWI domain proteins and Dicer. Tahbaz N, Kolb FA, Zhang H, Jaronczyk K, Filipowicz W, Hobman TC EMBO Rep 2004-01-01 (5) 14749716
Human RISC couples microRNA biogenesis and posttranscriptional gene silencing. Gregory RI, Chendrimada TP, Cooch N, Shiekhattar R Cell 2005-11-18 (123) 16271387
Identification of novel argonaute-associated proteins. Meister G, Landthaler M, Peters L, Chen PY, Urlaub H, Luhrmann R, Tuschl T Curr Biol 2005-12-06 (15) 16289642
TRBP, a regulator of cellular PKR and HIV-1 virus expression, interacts with Dicer and functions in RNA silencing. Haase AD, Jaskiewicz L, Zhang H, Laine S, Sack R, Gatignol A, Filipowicz W EMBO Rep 2005-10-01 (6) 16142218
A human, ATP-independent, RISC assembly machine fueled by pre-miRNA. Maniataki E, Mourelatos Z Genes Dev 2005-12-15 (19) 16357216
The role of PACT in the RNA silencing pathway. Lee Y, Hur I, Park SY, Kim YK, Suh MR, Kim VN EMBO J 2006-01-08 (25) 16424907
Human TRBP and PACT directly interact with each other and associate with dicer to facilitate the production of small interfering RNA. Kok KH, Ng MH, Ching YP, Jin DY J Biol Chem 2007-06-15 (282) 17452327
RNA helicase A interacts with RISC in human cells and functions in RISC loading. Robb GB, Rana TM Mol Cell 2007-05-25 (26) 17531811
MicroRNA silencing through RISC recruitment of eIF6. Chendrimada TP, Finn KJ, Ji X, Baillat D, Gregory RI, Liebhaber SA, Pasquinelli AE, Shiekhattar R Nature 2007-06-14 (447) 17507929
Prolyl 4-hydroxylation regulates Argonaute 2 stability. Qi HH, Ongusaha PP, Myllyharju J, Cheng D, Pakkanen O, Shi Y, Lee SW, Peng J, Shi Y Nature 2008-09-18 (455) 18690212
In vitro reconstitution of the human RISC-loading complex. MacRae IJ, Ma E, Zhou M, Robinson CV, Doudna JA Proc Natl Acad Sci U S A 2008-02-15 (105) 18178619
A TARBP2 mutation in human cancer impairs microRNA processing and DICER1 function. Melo SA, Ropero S, Moutinho C, Aaltonen LA, Yamamoto H, Calin GA, Rossi S, Fernandez AF, Carneiro F, Oliveira C, Ferreira B, Liu CG, Villanueva A, Capella G, Schwartz S Jr, Shiekhattar R, Esteller M Nat Genet 2009-03-01 (41) 19219043
Extending the phenotypes associated with DICER1 mutations. Foulkes WD, Bahubeshi A, Hamel N, Pasini B, Asioli S, Baynam G, Choong CS, Charles A, Frieder RP, Dishop MK, Graf N, Ekim M, Bouron-Dal Soglio D, Arseneau J, Young RH, Sabbaghian N, Srivastava A, Tischkowitz MD, Priest JR Hum Mutat 2011-12-01 (32) 21882293
Recurrent somatic DICER1 mutations in nonepithelial ovarian cancers. Heravi-Moussavi A, Anglesio MS, Cheng SW, Senz J, Yang W, Prentice L, Fejes AP, Chow C, Tone A, Kalloger SE, Hamel N, Roth A, Ha G, Wan AN, Maines-Bandiera S, Salamanca C, Pasini B, Clarke BA, Lee AF, Lee CH, Zhao C, Young RH, Aparicio SA, Sorensen PH, Woo MM, Boyd N, Jones SJ, Hirst M, Marra MA, Gilks B, Shah SP, Foulkes WD, Morin GB, Huntsman DG N Engl J Med 2012-02-19 (366) 22187960
DICER1 mutations in familial pleuropulmonary blastoma. Hill DA, Ivanovich J, Priest JR, Gurnett CA, Dehner LP, Desruisseau D, Jarzembowski JA, Wikenheiser-Brokamp KA, Suarez BK, Whelan AJ, Williams G, Bracamontes D, Messinger Y, Goodfellow PJ Science 2009-08-21 (325) 19556464
DICER1 mutations in familial multinodular goiter with and without ovarian Sertoli-Leydig cell tumors. Rio Frio T, Bahubeshi A, Kanellopoulou C, Hamel N, Niedziela M, Sabbaghian N, Pouchet C, Gilbert L, O'Brien PK, Serfas K, Broderick P, Houlston RS, Lesueur F, Bonora E, Muljo S, Schimke RN, Bouron-Dal Soglio D, Arseneau J, Schultz KA, Priest JR, Nguyen VH, Harach HR, Livingston DM, Foulkes WD, Tischkowitz M JAMA 2011-02-05 (305) 21205968



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Last modification of this entry: Sept. 25, 2012.

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