mtTF1: A Novel Factor Involved in Mitochondrial Gene Expression in Trypanosoma brucei

Mitochondrial DNA replication and gene expression are essential for cell survival. In Trypanosoma brucei, a protozoan animal and human parasite, the mitochondrial RNA polymerase (mtRNAP) plays roles in both transcription and DNA replication. This study identifies and characterizes the first mitochondrial transcription factor (mtTF1) in the Kinetoplastea. mtRNAP and mtTF1 form a high-molecular-weight complex that localizes to the kinetoplast DNA (kDNA) and is essential for parasite survival in both life cycle stages. Their localization is interdependent, and both proteins influence maxicircle replication, but not minicircle replication. Knockdown of either protein result in altered gene expression, particularly affecting the minor strand of the mitochondrial genome. Since mtTF1 is unique to the Kinetoplastea, it might prove to be a promising drug target. Study: AEKC-20231011 + AEKC-20250213; Libraries: AEKC-1-2 + AEKC-3-4; Run type: 2x150; Reference MK584625.1. fasta (T. brucei maxicircle sequence) and Tbrucei_EATRO1125.fasta (T. brucei minicircle sequence). Library ID and sample names: AEKC-1: mtRNAP_0d; AEKC-2: mtRNAP_2d; AEKC-3: mtTF1_0d and AEKC4: mtTF1_2d.