title: Constructive edge of uridylation-induced RNA degradation.
abstract: RNA uridylation is a significant transcriptome-shaping factor in protists, fungi, metazoans, and plants. The 3' U-additions are catalyzed by terminal uridyltransferases (TUTases), a diverse group of enzymes that along with non-canonical poly(A) polymerases form a distinct group in the superfamily of DNA polymerase β-like nucleotidyl transferases. Within and across studied organisms and subcellular compartments, TUTases differ in nucleotide triphosphate selectivity, interacting partners, and RNA targets. A general premise linking RNA uridylation to 3'-5' degradation received support from several studies of small RNAs and mRNA turnover. However, recent work on kinetoplastid protists typified by Trypanosoma brucei provides evidence that RNA uridylation may play a more nuanced role in generating functional small RNAs. In this pathogen's mitochondrion, most mRNAs are internally edited by U-insertions and deletions, and subjected to 3' adenylation/uridylation; guide RNAs (gRNAs) required for editing are U-tailed. The prominent role of uridylation in mitochondrial RNA metabolism stimulated identification of the first TUTase, RNA editing TUTase 1 (RET1). Here we discuss functional studies of mitochondrial uridylation in trypanosomes that have revealed an unorthodox pathway of small RNA biogenesis. The current model accentuates physical coupling of RET1 and 3'-5' RNase II/RNB-type exonuclease DSS1 within a stable complex termed the mitochondrial 3' processome (MPsome). In the confines of this complex, RET1 initially uridylates a long precursor to activate its 3'-5' degradation by DSS1, and then uridylates trimmed guide RNA to disengage the processing complex from the mature molecule. We also discuss a potential role of antisense transcription in the MPsome pausing at a fixed distance from gRNA's 5' end. This step likely defines the mature 3' end by enabling kinetic competition between TUTase and exonuclease activities.
authors.affiliation: a Department of Molecular and Cell Biology , Boston University School of Dental Medicine , Boston , MA , USA.|b Department of Biochemistry , Boston University School of Medicine , Boston , MA , USA.
authors.forename: Ruslan
authors.initials: R
authors.lastname: Aphasizhev
authors.affiliation: a Department of Molecular and Cell Biology , Boston University School of Dental Medicine , Boston , MA , USA.
authors.forename: Takuma
authors.initials: T
authors.lastname: Suematsu
authors.affiliation: c Section of Computational Biomedicine, Boston University School of Medicine , Boston , MA , USA.
authors.forename: Liye
authors.initials: L
authors.lastname: Zhang
authors.affiliation: a Department of Molecular and Cell Biology , Boston University School of Dental Medicine , Boston , MA , USA.
authors.forename: Inna
authors.initials: I
authors.lastname: Aphasizheva
mesh_terms: D005092:Exonucleases / Q000378:metabolism; D008928:Mitochondria / Q000235:genetics; D015800:Protozoan Proteins / Q000378:metabolism; D017393:RNA Editing; D012316:RNA Nucleotidyltransferases / Q000378:metabolism; D020871:RNA Stability; D017394:RNA, Guide, Kinetoplastida / Q000235:genetics; D012333:RNA, Messenger / Q000737:chemistry*; D016053:RNA, Protozoan / Q000737:chemistry / Q000378:metabolism; D058727:RNA, Small Untranslated / Q000378:metabolism*; D014345:Trypanosoma / Q000235:genetics*; D014529:Uridine / Q000378:metabolism*
chemical_list: D015800:Protozoan Proteins; D012333:RNA, Messenger; D016053:RNA, Protozoan; D058727:RNA, Small Untranslated; D012316:RNA Nucleotidyltransferases; C031687:UTP-RNA uridylyltransferase; D005092:Exonucleases; D014529:Uridine; D017394:RNA, Guide, Kinetoplastida
keywords: RNA decay; RNA editing; TUTase; Trypanosoma; exonuclease; guide RNA; mitochondria; uridylation