been observed as well, showing some similarities to flaviviral xrRNAs. However, plant-virus xrRNA and flaviviral xrRNA are distinguishable by their underlying three-dimensional folds. Dumbbell element The dumbbell element (DB) are important for viral RNA synthesis. Via the formation of additional pseudoknots, the loop regions of DB pairs with a complementary motif further downstream of the respective DB element. The DB elements also expose conserved sequences (CS) and repeated conserved sequences (RCS). Further, the DB elements are also playing a role in viral translation, as deletion of both elements reduced viral translation levels. Pseudoknot-forming stem-loops There is evidence that pseudoknot-forming stem-loops (SL-PK) are encoded by dual-host insect-specific flaviviruses and classical insect-specific flaviviruses but while short stem-loops are present in the genomes of all mosquito-borne flaviviruses, they are not involved in pseudoknot interactions for which structural is available. It is thought that SL-PK might stabilise xrRNAs or confer additional XRN1 resistance as abolishing the SL-PK of various viruses reduces the production of sfRNAs. CRE structure The cis-acting replication element (CRE) structure is structurally conserved among known flaviviruses. It consists of a small hairpin (sHP) and a larger structural element (3'SL). Mutations of sHP are shown to be lethal for Dengue virus in mosquito cells. CRE is highly involved in the 5'-3' UTR interaction of flaviviruses. Regions of sHP are interacting with the SLB element and the cHP in the 5' UTR, whereas the 3'SL harbors a sequence that can interact with SLB, to further stabilize this long-range RNA-RNA interaction. Repeated elements In ISFV, structural alignments of the 3' UTR revealed that many species harbor three to four repeats of two highly conserved elements, termed Ra and Rb. These elements show variable loop regions and low sequence conservation in the Ra element. However, strong structure conservation and the occurrence of multiple copies may hint towards a possible functional importance of these elements. SL6 short hairpin In different studies, a short stem-loop, named SL6 has been observed in at least TBEV, LGTV and OHFV. SL6 shows a high heterogeneity among different tick-borne flaviviruses, but is structurally conserved supported by multiple covariation. References Non-coding RNA Flaviviridae