DIFFERENTIAL EXPRESSION OF LEISHMANIA-MAJOR BETA-TUBULIN GENES DURINGTHE ACQUISITION OF PROMASTIGOTE INFECTIVITY

Tubulin expression has been analysed as the insect stage of the protoz oan parasite Leishmania major differentiates from a non-infective to a n infective form. This transformation of the promastigote stage occurs in vitro and analysis of beta-tubulin mRNA expression in axenically g rown promastigotes showed that a 2200 nt transcript is predominately e xpressed in non-infective promastigotes. The message contains a motif associated with mRNA intracellular localisation and its level is reduc ed by an order of magnitude in infective promastigotes through a mecha nism involving RNA stability. A 3200 nt RNA, the major beta-tubulin tr anscript in the infective stage, is encoded by a single copy gene at t he 3' end of the array that encodes the 2200 nt RNA. These RNAs, as we ll as a gene encoding a beta-tubulin transcript highly up-regulated in the mammalian stage of the parasite, encode polypeptides that are app arently functionally equivalent but have highly diverged 3' untranslat ed regions. This differential regulation of the dispersed isogenes may reflect the involvement of a mechanism altering tubulin synthesis dur ing the Leishmania life cycle. The analysis of alpha-tubulin RNA level s revealed the abundance of this message falls as promastigotes differ entiate into an infectious stage and the transcript is destabilised in infective promastigotes. These data demonstrate that the regulation o f mRNA half-life contributes to controlling gene expression as promast igotes differentiate into an infectious form.