Inna Afasizheva

Education

PhD (Molecular Biology), Russian Academy of Sciences, 1995; MS (Biophysics), Moscow State University, 1992; BS (Biophysics), Moscow State University, 1991

Research Description

Our research program is focused on mechanisms and regulation of mitochondrial RNA processing in Trypanosoma brucei. Diseases caused by these unicellular parasites inflict health hazards and economic hardship on many impoverished counties in Sub-Saharan Africa. Failing vector control and the rise of drug-resistance necessitate a search for new drugs targets with emphasis on parasite-specific processes. Mitochondrial RNA processing pathways in trypanosomes are extremely divergent from those of humans and represent a rich source of therapeutic intervention points. Our lab has made significant contributions to establishing critical roles of uridine insertion/deletion mRNA editing, polyadenylation and uridylation to mitochondrial gene expression. We discovered key enzymes involved in maturation, stabilization and translational activation of mitochondrial messenger RNAs: RET1 terminal uridyltransferase and KPAP1 poly(A) polymerase. These enzymes function by adding uridine and adenosine residues, respectively, to mRNA 3’ ends. However, the mechanisms regulating these activities remain largely unknown. Recently we found that polyadenylation and translation complexes are populated by members of a diverse family of pentatricopeptide repeat RNA binding proteins (PPRs). Originally discovered in plant organelles, PPRs are involved in many aspects of RNA processing; to that end, trypanosomal genomes contain perhaps the largest collection of PPR genes among non-plant organelles. Our research program is concentrated on three major areas: 1) The role of PPRs in general and transcript specific mRNA adenylation/uridylation; 2) Principles of uridylation-based mRNA decay and 3) PPR functions in mRNA 3’ definition. Our approaches include biochemistry, genetics, proteomics, crystallography, deep sequencing, ribosome profiling and bioinformatics. The research is funded by National Institute of Allergy and Infectious Diseases.