Inhibition of mRNA maturation in trypanosomes causes the formation of novel foci at the nuclear periphery containing cytoplasmic regulators of mRNA fate

Maturation of all cytoplasmic mRNAs in trypanosomes involves trans-splicing of a short exon at the 5′ end. Inhibition of trans-splicing results in an accumulation of partially processed oligocistronic mRNAs. Here, we show that the accumulation of newly synthesised partially processed mRNAs results in the formation of foci around the periphery of the nucleus. These nuclear periphery granules (NPGs) contain the full complement of P-body proteins identified in trypanosomes to date, as well as poly(A)-binding protein 2 and the trypanosome homologue of the RNA helicase VASA. NPGs resemble perinuclear germ granules from metazoa more than P-bodies because they: (1) are localised around the nuclear periphery; (2) are dependent on active transcription; (3) are not dissipated by cycloheximide; (4) contain VASA; and (5) depend on nuclear integrity. In addition, NPGs can be induced in cells depleted of the P-body core component SCD6. The description of NPGs in trypanosomes provides evidence that there is a perinuclear compartment that can determine the fate of newly transcribed mRNAs and that germ granules could be a specialised derivative.