**5. Conclusion**

532 A Bird's-Eye View of Veterinary Medicine

interesting issue, given its intermediary position between Bovidae-Cervidae group and the Camelidae. Consequently, it is not possible to assign a specific role of the LDCBC and or of the 3 insertions to the stability of *Prnp* RNA. Their potential influence will be assessed

As explained in introduction, several types of potential target sites of micro-RNAs are to be explored according to their position relatively to the LDCBC: (i) between the stop codon and the LDCBC (all Mammals), (ii) in the sequence corresponding to the LDCBC (all Mammals except Bovidae-Cervidae), and (iii) in the inserted elements particular to Bovidae-Cervidae. Generally, miRNAs inhibit protein synthesis either by the repression of the translation and/or by the activation of the deadenylation leading to the degradation of the targeting mRNA (Eulalio et al., 2008; Chekulaeva & Filipowicz, 2009). Multiples sites, either for the same or different miRNAs, are usually required for a more effective repression, and they tend to act cooperatively when they are close to each other (Doench et al., 2004; Grimson et al., 2007). As most microRNA play a role in repression, a special attention will be brought to targets present in most mammals but absent in Bovidae-Cervidae. However, targets restricted to Bovidae-Cervidae could have significance through an activating role in stability

In the sequence comprised between stop codon and LDCBC, the most spread target within mammals corresponds the group Mir-3918/509-519. According to fig. 3, this target is situated in one of the most conservative regions in 3'UTR of PRNP gene. Its possible involvement could be interpreted as the result of an under-expression of the corresponding Mirs in Bovidae-Cervidae, according to the second type mentioned in introduction section.

In the sequence corresponding to the large deletion common to Bovidae-Cervidae, two targets are interesting to consider, corresponding to Mir4763 and Mir-15B/369. According to literature, Mir15b belong to a small family of Mirs comprising also Mir15a, Mir16a, Mir16b, and Mir195 in Mammals. Interestingly, Mir15b as well as Mir15a have proved to be involved as repressing cancers in human. It has been shown an association between deletion of Mir15a gene, together with Mir16 in the same cluster in HSA chromosome 13q14, and pituitary tumors (Bottoni et al., 2005). The same authors showed that the expression level of these 2 Mirs is inversely correlated to the pituitary adenoma growth. Another study of Calin et al., 2002 showed that deletions in the same cluster of Mir 15b-Mir16 are associated to chronic lymphocytic leukemia. Similarly, a high expression level of Mir15b is linked to a low proliferation of hepatocellular carcinoma (Chung et al., 2010). As for Mir369, Williams et al. (2007) showed that members of family Mir-154 are especially expressed in mouse and

The presence of transposable elements in the *Prnp* transcript of Bovidae and Cervidae is an interesting feature. It is unlikely that they contribute to the stability of mRNA, as no publications support this view. However, these transposable elements contain putative targets for Mirs that confer new possibility of regulation, as shown in mammals (Smalheiser & Torvik, 2005). These putative Mirs could play a role in the stability of *Prnp* gene. We could bring the same hypothesis to the targets of Mir-569/155, 376, 15b, present in the region

independently.

of transcript (Vasudevan et al., 2007).

human foetal, but not adult, lung.

proximal to stop codon.

It would be interesting to test experimentally this idea.

The 3'-UTR sequence of *Prnp* gene is well conserved with Eutherians, and especially in the first 600 pb downstream to stop codon, suggesting a role in regulation of stability of the mRNA. In the 3'-UTR part of *SPRN*, a gene close to *Prnp*, Premzl & Gamulin (2007) showed a target for Mir-34a shared by several orders of mammals. It is unlikely that such a unique target is present in the case of mammalian *Prnp*. Our analyses rather suggest an interaction between several targets which could modulate the stability of this transcript. The combination of acting Mirs could vary among mammals and the high sensitivity of Bovidae and Cervidae could be explained by the lack of several key targets.
