Modulation of the Host Nuclear Compartment by Trypanosoma cruzi Uncovers Effects on Host Transcription and Splicing Machinery

• DOI: 10.3389/fcimb.2021.718028
• Publication Date: 2021-10-20T20:42:48Z
• Authors: Camila Gachet-Castro; Felipe Freitas-Ca...; Raul Alexander Go...; Carol Kobori da F...; Marcelo Damário G...; Hellen Cristina I...; Munira Muhammad A...
• Keywords: Transcription; Host factors

Host manipulation is a common strategy for invading pathogens. Trypanosoma cruzi, the causative agent of Chagas Disease, lives intracellularly within host cells. During infection, parasite-associated modifications occur to cell metabolism and morphology. However, little known about effect T. cruzi infection on nucleus nuclear functionality. Here, we show that can modulate transcription splicing machinery in non-professional phagocytic cells during infection. We found regulates RNA polymerase II (RNAPII) time-dependent manner, resulting drastic decrease RNAPII activity. Furthermore, ribonucleoproteins associated with mRNA (hnRNPA1 AB2) are downregulated concurrently. reasoned may hijack U2AF35 auxiliary factor, key regulator processing, as affect activities directly. In support our hypothesis, carried out vivo assays using an adenovirus E1A pre-mRNA reporter, showing intracellular directly modulates by appropriating U2AF35. For first time, results provide evidence complex intimate molecular relationship between