The aim of this study was to generate and analyze the atlas of the loggerhead turtle blood transcriptome by RNA-seq, as well as identify and characterize thioredoxin (Tnxs) and peroxiredoxin (Prdxs) antioxidant enzymes of the greatest interest in the control of peroxide levels and other biological functions. The transcriptome of loggerhead turtle was sequenced using the Illumina Hiseq 2000 platform and de novo assembly was performed using the Trinity pipeline. The assembly comprised 515,597 contigs with an N50 of 2,631 bp. Contigs were analyzed with CD-Hit obtaining 374,545 unigenes, of which 165,676 had ORFs encoding putative proteins longer than 100 amino acids. A total of 52,147 (31.5%) of these transcripts had significant homology matches in at least one of the five databases used. From the enrichment of GO terms, 180 proteins with antioxidant activity were identified, among these 28 Prdxs and 50 putative Tnxs. The putative proteins of loggerhead turtles encoded by the genes Prdx1, Prdx3, Prdx5, Prdx6, Txn and Txnip were predicted and characterized in silico. When comparing Prdxs and Txns of loggerhead turtle with homologous human proteins, they showed 18 (9%), 52 (18%) 94 (43%), 36 (16%), 35 (33%) and 74 (19%) amino acid mutations respectively. However, they showed high conservation in active sites and structural motifs (98%), with few specific modifications. Of these, Prdx1, Prdx3, Prdx5, Prdx6, Txn and Txnip presented 0, 25, 18, three, six and two deleterious changes. This study provides a high quality blood transcriptome and functional annotation of loggerhead sea turtles.

Hereditary leiomyomatosis and renal cell cancer syndrome (HLRCC) is a very rare disease that is inherited in an autosomal dominant manner. Affected patients may develop from cutaneous and uterine leiomyomas to type 2 papillary renal cell carcinoma (Schmidt and Linehan, Int J Nephrol Renovasc Dis 7:253-260, 2014). HLRCC is caused by germline mutations in the FH gene, which produces the fumarate hydratase protein that participates in the tricarboxylic acid cycle during the conversion of fumarate to malate. In FH-deficient cells, high concentrations of fumarate lead to a series of intricate events, which seem to be responsible for the malignant transformation (Yang et al., J Clin Invest 123(9):3652-3658, 2013) (Bardella et al., J Pathol 225(1):4-11, 2011). Among these events, one that is gaining attention is the pathological activation of the nuclear factor erythroid 2-related factor 2 (NRF2) pathway, which has been found in several types of cancer and is implicated in the expression of genes associated with antioxidant responses (Linehan and Rouault, Clin Cancer Res 19(13):3345-3352, 2013). In this article, we present the results of a gene expression analysis performed on peripheral blood cells from patients with HLRCC syndrome, where upregulation of numerous NRF2 targets and the differential expression of two key genes, Jun dimerization protein 2 (JDP2) and Phosphoglycerate mutase family member 5 (PGAM5), which are involved in the control of this pathway, was observed.

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