Topoisomerase research of kinetoplastid parasite Leishmania, with special reference to development of therapeutics.

Protozoan parasites of the order Kinetoplastida cause severe diseases primarily in the tropical and subtropical areas. The enormous development of molecular and cellular biology in recent times have provided opportunities for discovering newer molecular targets for drug designing, which now form a rational basis for the development of improved anti-parasitic therapy. DNA topoisomerases play a key role in cellular processes affecting the topology and organization of intracellular DNA. Recently, emergence of the bi-subunit topoisomerase I in the kinetoplastid family has brought a new twist in topoisomerase research related to evolution, functional conservation and as a potential target that can be exploited in drug designing and development of new intervention strategies. This review summarizes the biology of kinetoplastid topoisomerases, which are the key molecular targets in antileishmanial chemotherapy.

Generation of bacteriophage T3 mRNAs by post-transcriptional processing by RNase III.

The primary transcripts synthesized in vitro from a T3 DNA template by Escherichia coli RNA polymerase and by T3 phage-specific RNA polymerase have been characterized with regard to cleavage by RNase III and the size of the products of the cleavage reaction have been compared with those of in vivo T3 RNAs. It has been observed that the large RNA molecule synthesized in vitro by Escherichia coli RNA polymerase from the early region of T3 DNA are cleaved at specific sites by Escherichia coli RNase III to produce all the early mRNAs normally observed in T3-infected cells. In contrast, evidence presented here shows that some of the late T3 mRNAs are generated as direct products of transcription of late regions of T3 DNA by T3 RNA polymerase without mediation of RNase III, while many other late T3 mRNAs are formed by RNase III cleavage of two of the high molecular weight T3 RNA polymerase transcripts. These in vitro data appear to be in good agreement with the observed sizes of late T3 mRNAs formed in vivo in T3-infected RNase III-deficient and RNase III+ Escherichia coli cells.