# STOCKHOLM 1.0 #=GF ID Flavi_NKV_xrRNA #=GF AC RF03539 #=GF DE No-known vector Flavivirus exoribonuclease-resistant RNA element #=GF AU Lamkiewicz K; 0000-0002-6375-6441 #=GF GA 50.0 #=GF NC 38.4 #=GF TC 82.8 #=GF SE Lamkiewicz K #=GF SS Predicted; LocARNA 2.0.0RC8 #=GF TP Cis-reg; #=GF BM cmbuild -F CM SEED #=GF CB cmcalibrate --mpi CM #=GF SM cmsearch --cpu 4 --verbose --nohmmonly -T 30.00 -Z 2958934 CM SEQDB #=GF DR SO; 0000837; UTR_region; #=GF RN [1] #=GF RM 19064258 #=GF RT A highly structured, nuclease-resistant, noncoding RNA produced by #=GF RT flaviviruses is required for pathogenicity. #=GF RA Pijlman GP, Funk A, Kondratieva N, Leung J, Torres S, van der Aa L, Liu #=GF RA WJ, Palmenberg AC, Shi PY, Hall RA, Khromykh AA #=GF RL Cell Host Microbe. 2008;4:579-591. #=GF RN [2] #=GF RM 23006624 #=GF RT A noncoding RNA produced by arthropod-borne flaviviruses inhibits the #=GF RT cellular exoribonuclease XRN1 and alters host mRNA stability. #=GF RA Moon SL, Anderson JR, Kumagai Y, Wilusz CJ, Akira S, Khromykh AA, Wilusz J #=GF RL RNA. 2012;18:2029-2040. #=GF RN [3] #=GF RM 25635835 #=GF RT Dengue virus RNA structure specialization facilitates host adaptation. #=GF RA Villordo SM, Filomatori CV, Sanchez-Vargas I, Blair CD, Gamarnik AV #=GF RL PLoS Pathog. 2015;11:e1004604. #=GF RN [4] #=GF RM 28587300 #=GF RT The 5' and 3' Untranslated Regions of the Flaviviral Genome. #=GF RA Ng WC, Soto-Acosta R, Bradrick SS, Garcia-Blanco MA, Ooi EE #=GF RL Viruses. 2017; [Epub ahead of print] #=GF RN [5] #=GF RM 18701589 #=GF RT A viral noncoding RNA generated by cis-element-mediated protection against #=GF RT 5'->3' RNA decay represses both cap-independent and cap-dependent #=GF RT translation. #=GF RA Iwakawa HO, Mizumoto H, Nagano H, Imoto Y, Takigawa K, Sarawaneeyaruk S, #=GF RA Kaido M, Mise K, Okuno T #=GF RL J Virol. 2008;82:10162-10174. #=GF RN [6] #=GF RM 29866852 #=GF RT A folded viral noncoding RNA blocks host cell exoribonucleases through a #=GF RT conformationally dynamic RNA structure. #=GF RA Steckelberg AL, Akiyama BM, Costantino DA, Sit TL, Nix JC, Kieft JS #=GF RL Proc Natl Acad Sci U S A. 2018;115:6404-6409. #=GF RN [7] #=GF RM 32848042 #=GF RT The crystal structure of a Polerovirus exoribonuclease-resistant RNA shows #=GF RT how diverse sequences are integrated into a conserved fold. #=GF RA Steckelberg AL, Vicens Q, Costantino DA, Nix JC, Kieft JS #=GF RL RNA. 2020; [Epub ahead of print] #=GF CC The exoribonuclease-resistant RNA elements (xrRNA) are described #=GF CC throughout all groups of flaviviruses. Usually, each virus harbors two #=GF CC xrRNAs, xrRNA1 and xrRNA2, in the beginning of the 3' UTR [1]. The #=GF CC formation of these stem-loops, especially xrRNA1, is vital to ensure #=GF CC resistance against XRN1 activity [2]. The Y-shaped stem-loop is also #=GF CC termed SL II and SL IV, respectively. In order to function as xrRNA, the #=GF CC sequence downstream is needed as well, since the upper loop region forms a #=GF CC pseudoknot (PK) with the single-stranded region directly downstream to its #=GF CC respective hairpin. In some species, the region downstream also forms a #=GF CC small hairpin. In such cases, the PK interactions takes place between the #=GF CC two loop regions. Conserved formation of these structures were observed in #=GF CC mammalian cells but not in mosquito cells, suggesting this region has #=GF CC varying functions in different hosts[3][4]. In plant-viruses, xrRNA #=GF CC elements have been observed as well, showing some similarities to #=GF CC flaviviral xrRNAs[5][6]. However, plant-virus xrRNA and flaviviral xrRNA #=GF CC are distinguishable by their underlying three-dimensional folds[7]. #=GF WK Flavivirus_3'_UTR #=GF SQ 3 NC_003635.1/10257-10338 GAGUGUUGAGGGCAACCAGUGGGCUAGCCACA----UGGGUAUGACGCACCCA---CCCUCUGCAUUC-UUGUAAAUACUUUGGCCAGUC- NC_004119.1/10281-10362 UGCGAGUGAGGGCAACUCUGGGAUUAGCUCAA----UGGGUGUGACGACCCUA---CCCUU--CCGCAUUUGUAAAUAAUUGAGCCAGUCA NC_005039.1/10454-10530 AA-GUGUCAGGCCAA---GAUUGAGAAAAUCUUGCCACAGCUUGGCAGACUGUGCAGCCUGCAGCCCUAGAGGGAG----------ACUGA #=GC SS_cons (((((--(((((,,,,,,<<<<_____>>>>,....<<<<-<<____>>>>>>...)))))--)))))::::::::::::::::::::::: #=GC RF ggcgggUgAGGgCAACuaggggGuuAgcccca....ugGGUguGACgacCCca...cCCUcuaccgccauuGuAAAUAaUUuaGCCAgUcA //