Mitochondrial RNA quality control in trypanosomes

Abstract

Unicellular parasites Trypanosoma brucei spp. cause African human and animal trypanosomiasis, a spectrum of diseases that jeopardize public health and afflict the economy in sub‐Saharan Africa. These hemoflagellates are distinguished by a single mitochondrion, which contains a kinetoplast nucleoid composed of DNA and histone‐like proteins. Kinetoplast DNA (kDNA) represents a densely packed network of interlinked relaxed circular molecules: a few ~23‐kb maxicircles encoding ribosomal RNAs (rRNAs) and proteins, and approximately 5,000 1‐kb minicircles bearing guide RNA (gRNA) genes. The transcription start site defines the mRNA's 5′ terminus while the primary RNA is remodeled into a monocistronic messenger by 3′–5′ exonucleolytic trimming, 5′ and 3′ end modifications, and, in most cases, by internal U‐insertion/deletion editing. Ribosomal and guide RNA precursors are also trimmed, and the processed molecules are uridylated. For 35 years, mRNA editing has attracted a major effort, but more recently the essential pre‐ and postediting processing and turnover events have been discovered and the key effectors have been identified. Among these, pentatricopeptide repeat (PPR) RNA binding proteins emerged as conduits coupling modifications of mRNA termini with internal sequence changes introduced by editing. Among 39 annotated PPRs, 20 belong to ribosomal subunits or assembly intermediates, four function as polyadenylation factors, a single factor directs 5′ mRNA modification, and one protein is found in F1‐ATPase. Nuclear and mitochondrial RNases P consist of a single PPR polypeptide, PRORP1 and PROP2, respectively. Here, we review PPR‐mediated mitochondrial processes and discuss their potential roles in mRNA maturation, quality control, translational activation, and decay. This article is categorized under: RNA Processing > Capping and 5′ End Modifications RNA Processing > 3′ End Processing RNA Processing > RNA Editing and Modification

KREH2 helicase represses ND7 mRNA editing in procyclic-stageTrypanosoma bruceiby opposite modulation of canonical and “moonlighting” gRNA utilization creating a proposed mRNA structure

“…KREH2 may also modulate editing guided by specific gRNA bases outside the classified guiding regions in other guides, as shown for conserved terminal adenines in initiator gRNAs in ND7 3’ in this study, and in RPS12 in a prior study (13). Although KREH2 may control gRNA usage or even usage of specific bases in a gRNA, mRNA turnover control may also be important during development (72). The frequency of gRNAs, cognate or non-cognate, or mRNA-gRNA duplex thermodynamic stability (predicted ι1G) may not be critical determinants in developmental ND7 3’ control.…”

Mitochondrial RNA editing in Trypanoplasma borreli: New tools, new revelations

“…However, sequencing the T. borreli gRNA population in the future would still be valuable: T. borreli gRNAs were reported to uniquely possess non-encoded oligo(U) sequence on both their 5′ and 3′ termini [37] . As gRNAs of other species invariably carry only non-encoded 3′ oligo(U) extensions [77] , exploring this difference could lead to insights regarding gRNA processing.…”

Multiple structural flavors of RNase P in precursor tRNA processing

“…Trypanosoma brucei belongs to the eukaryotic parasitic kinetoplastids responsible for serious diseases in humans, which are an excellent model system to study various aspects of eukaryotic cell biology (Aphasizheva & Aphasizhev, 2021;Matthews, 2005). Early work using purified T. brucei mitochondrial extracts revealed RNase P-like activity by an enzyme of $70 kDa that lacks an RNA component (Salavati et al, 2001).…”

“…Trypanosoma brucei belongs to the eukaryotic parasitic kinetoplastids responsible for serious diseases in humans, which are an excellent model system to study various aspects of eukaryotic cell biology (Aphasizheva & Aphasizhev, 2021; Matthews, 2005). Early work using purified T .…”