Chinese Journal of Biochemistry and Molecular Biology ; (untranslated region,utr) (internal ribosome entry site, IRES). ,.

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1 ISSN CN ΠQ Chinese Journal of Biochemistry and Molecular Biology 23 (7) : RNA ( IRES),,,, (, ;, ) 3 RNA 5 (untranslated region,utr) (internal ribosome entry site, IRES), mrna, IRES RNA,, RNA IRES,, RNA IRES RNA ; ( IRES) ; Q IRES : Translation Element of RNA Viruses LU Jie, ZHANGJia2Min, LIN Mei2Juan, CAO Xu, HU Yuan2Yang 3 ( State Key Laboratory of Virology, College of Life Sciences, Wuhan University, Wuhan , China ; Global BioPesticide Limited & Wuhan University Joint Research & Development Centre, Wuhan , China) Abstract Initiation translation of most eukaryotic mrnas occurs by cap2dependent translation However, a group of positive sense RNA viruses lacking cap structures can initiate the translation by a cis2element in the 5 untranslated region internal ribosome entry site ( IRES) They can recruit ribosome subunits to the start site of viral mrna with the aid of certain trans2acting factors To date, RNA viruses of IRES2dependent translation initiation are discovered in the mammals, invertebrates and plants IRES elements are grouped in four classes based on the different structure and function The further study of IRES elements in the RNA viruses will not only help the understanding viral pathogenesis, but also provide the guidance for the industrial application and disease therapy The review focuses on the discovery, classes, structure and function of IRES elements,respectively Key words RNA virus ; internal ribosome entry site ( IRES) ; translation initiation RNA, mrna ( EMVC), (CSFV), IRES 20, (TEV) ( HAV),, 1 IRES mrna,, RNA 5 : , : (No ) 3 Tel : ,E2mail : edu cn (untranslated region,utr) Received : December 18,2006, Accepted :April 23, 2007 ( internal ribosome entry Supported by National Natural Science Foundation of China (No ) site, IRES) 3 Corresponding author Tel : ,E2mail : edu cn

2 mrna 5 m 7 GpppN, (cap2dependent translation) [1 40S eif4f, RNA, RNA, eif4f eif4g, 5 eif4e ATP RNA eif4a VPg RNA,VPg eif3,eif4f mrna 40S 5 pu mrna, eif4g, AUG 5 A ( PABP) 3 A 5 AUG,, Kozak,5 RNA 5 3 ( Fig11B,C), [2 AUG Fig 1 Cap2dependent and IRES2dependent translation [ 2] (A) Cap2dependent translation requires a set of protein factors that interact with the 5 cap structure, then scanning to appropriate downstream AUG and translation ; (B) Schematic diagrams of a dicistronic mrna used for identifying IRES elements The assays utilized dicistronic mrnas containing two reporter genes, A and B ; (C) IRES2dependent translation requires viral RNA IRES and certain trans2acting factors to recruite the 43S preinitiation complex Complex RNA and protein interactions appear to allow the 40S ribosome and ternary complex to bypass multiple upstream AUG sequences, thus directing viral polyprotein synthesis at the appropriate downstream AUG 1988,Jang [3 ] ( EMCV) 5 UTR (PV) 5 UTR, A EMCV 5 (Fig11B) 5 UTR, B, B

3 7 :RNA ( IRES) 515, A eif4g eif3 eif4a, EMCV 5 UTR B 43S (Fig11C) EMCV 5 UTR 2 IRES RNA ( IRES), IRES RNA,Pelletier PV 5 UTR 1 IRES [4 eif4e, Table 1 Table 1 RNA viruses of IRES2dependent translation initiation,, Family Genus Strain Host Picornaviridae Enterovirus Human poliovirus 1 Human coxsackievirus B3 (CVB3) Bovine enterovirus (BEV) Rhinovirus Human rhinovirus ( HRV) Hepatovirus Hepatitis A virus ( HAV) Cardiovirus Encephalomyocarditis virus ( EMCV) Theiler s murine encephalomyelitis virus ( TMEV) Aphthovirus Foot2and2mouth disease virus ( FMDV) Erbovirus Equine rhinitis A virus ( ERAV) Equine rhinitis B virus ( ERBV) Parechovirus Human parechoviruses ( HPeV) Teschovirus Porcine teschovirus21 ( PTV) Talfan Dicistroviridae Cripavirus Plautia stali intestine virus ( PSIV) Invertebrate Rhopalosiphum padi virus (RhPV) Cricket paralysis virus (CrPV) Invertebrate Invertebrate? Iflavirus Ectropis oblique picorna2like virus ( EoPV) Invertebrate Varroa destructor virus 1 (VDV21) Invertebrate Flaviviridae Pestivirus Bovine viral diarrhea virus (BVDV) Classical swine fever virus (CSFV) Hepacivirus Hepatitis C virus ( HCV) GB virus B ( GBV2B)? Tobamovirus Crucifer tobamovirus (crtmv) Tobacco mosaic virus ( TMV) U1 Potyviridae Potyvirus Tobacco etch virus ( TEV) Plum pox virus ( PPV) Potato virus Y ( PVY) Turnip mosaic virus ( TuMV) Comoviridae Comovirus Cowpea mosaic virus (CPMV) Luteoviridae Polerovirus Potato leafroll virus ( PLRV) Datas from NCBI (http :ΠΠwww ncbi nlm nih govπ) and Web (http :ΠΠifr31w3 toulouse inserm frπires database) 3 IRES (enterovirus) ( rhinovirus),, IRES 4 IRES, (Fig12) : (Cardiovirus) (RRL), (Aphthovirus), H2L [9 12 HeLa, nt PV IRES AUG (hepatovirus) ( HAV), [6 8 (RRL) EMCV IRES IRES, ;

4 (RRL) (pestivirus) (CSFV), [13,14 ] [15,16 HCV (dicistroviridae) IRES, (CrPV) IRES, [17 (hepacivirus) ( HCV) 40S Fig 2 Types of IRES elements [ 5] Structural representation of the 5 UTR from EMCV (A), Poliovirus (B), HAV (C) and HCV (D) The region encompassing the IRES is underlined Pyrimidine2rich sequence elements( ) and translation initiation codon (AUG) are indicated nt AUG ], Y n X m 4 IRES IRES : PV IRES RNA,, (UUUCC) PV IRES, mrna 5 UTR UUUCC UAAAC, IRES PV 2 % EMCV TMEV IRES RNA 5, GC,, EMCV A, 30 % [9,18,19 IRES, IRES, RNA IRES [20 GC IRES, (Fig13) RNA IRES IRES GNRA (N,R ),C (C2rich motif) GNRA IRES,, EMCV PV IRES, RNA IRES GNAR C eif4f eif4g, IRES RNA IRES Y n - X m - AUG [ Y n (polypyrimidine tract) ; n = 5 7 nt X m (spacing), m 20 IRES,,, RNA IRES 40 S 3 : (1) EMCV IRES, eifs 2

5 7 :RNA ( IRES) 517 Fig 3 Schematic representation of picornaviral IRES [ 22] Conserved elements, namely, the polypyrimidine tract, the GNRA tetraloop (stem2loop A) and C2rich motif (loop B) are indicated Host encoded IRES2trans2acting factors (X and Y) may also be required to stabilize the structures or facilitate ribosome binding 3 4B, IRES eif4gπeif4a, IRES HCV, 40 S IRES ; (2), HCV IRES eif4a [23,24 B12 IRES, [25 eifs, eif22 HCV IRES PV IRES GTP2tRNAi, trna P PV (3) CrPV IRES 80S,, [4,26 eifs trna, IRES P [21 IRES IRES RNA, IRES,, eif4e (4EBP) eif4e, eif4g, NIH 3T3 4EBP, 293,, ( Gag Pol Env) [27 EMCV IRES [20 5 IRES [29 RNA IRES, RhPV IRES IRES RNA [30,IRES, IRES,, IRES ( HCV, IRES IL22) ( ) 2 [31 RNA, RNA IRES (aptamer) HCV IRES, RNA, HCV IRES 2, [28 ], IRES (adeno2associated virus, AAV) 2

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