Trypanosoma cruzi Ikiakarora (TcIII) Draft Genome Sequence.

Trypanosoma cruzi shows a genetic diversity that has been associated with the variability of clinical manifestations, geographical distribution, and preferential parasite-vector interactions. In an effort to better understand this genetic variability, here, the draft genome of T. cruzi strain Ikiakarora (discrete typing unit TcIII), which has been associated with the sylvatic cycle, is reported.

Draft Genome Sequence of the Trypanosoma cruzi B. M. López Strain (TcIa), Isolated from a Colombian Patient.

Trypanosoma cruzi parasite strains are classified into six lineages (discrete typing units TcI to TcVI). The broad genetic diversity of T. cruzi strains has an influence on the development of the host response and pathogenesis, as well as drug susceptibility. Here, the draft genome of the T. cruzi B. M. López strain (TcIa) is reported.

The wide expansion of hepatitis delta virus-like ribozymes throughout trypanosomatid genomes is linked to the spreading of L1Tc/ingi clade mobile elements.

BACKGROUND: Hepatitis Delta Virus (HDV)-like ribozymes have recently been found in many mobile elements in which they take part in a mechanism that releases intermediate RNAs from cellular co-transcripts. L1Tc in Trypanosoma cruzi is one of the elements in which such a ribozyme is located. It lies in the so-called Pr77-hallmark, a conserved region shared by retrotransposons belonging to the trypanosomatid L1Tc/ingi clade. The wide distribution of the Pr77-hallmark detected in trypanosomatid retrotransposons renders the potential catalytic activity of these elements worthy of study: their distribution might contribute to host genetic regulation at the mRNA level. Indeed, in Leishmania spp, the pervasive presence of these HDV-like ribozyme-containing mobile elements in certain 3'-untranslated regions of protein-coding genes has been linked to mRNA downregulation. RESULTS: Intensive screening of publicly available trypanosomatid genomes, combined with manual folding analyses, allowed the isolation of putatively Pr77-hallmarks with HDV-like ribozyme activity. This work describes the conservation of an HDV-like ribozyme structure in the Pr77 sequence of retrotransposons in a wide range of trypanosomatids, the catalytic function of which is maintained in the majority.These results are consistent with the previously suggested common phylogenetic origin of the elements that belong to this clade, although in some cases loss of functionality appears to have occurred and/or perhaps molecular domestication by the host. CONCLUSIONS: These HDV-like ribozymes are widely distributed within retrotransposons across trypanosomatid genomes. This type of ribozyme was once thought to be rare in nature, but in fact it would seem to be abundant in trypanosomatid transcripts. It can even form part of the pool of mRNA 3'-untranslated regions, particularly in Leishmania spp. Its putative regulatory role in host genetic expression is discussed.

Inhibition of HIV-1 replication by an improved hairpin ribozyme that includes an RNA decoy.

An anti-Tat hairpin ribozyme and a TAR RNA decoy were combined in one molecule. The chimeric molecule strongly inhibited HIV-1 replication (measured as changes in p24 levels in viral replication assays). The inhibitory action of the ribodecozyme (85%) was significantly greater than that shown by ribozyme and a non-catalytic variant carrying the functional decoy RNA domain (55% and 35%, respectively). This represents a significant improvement of the inhibitory efficiency of the ribozyme, suggesting there is an additive inhibitory effect on HIV-1 replication by the catalytic and decoy domains. This strategy could be used to create new inhibitor RNAs with enhanced in vivo performance.