Constructive edge of uridylation-induced RNA degradation. Issue 11 (1st November 2016)

• Record Type: Journal Article
• Authors: Aphasizhev, Ruslan; Suematsu, Takuma; Zhang, Liye; Aphasizheva, Inna
• Is Part Of: RNA biology. Volume 13:Issue 11(2016)
• Page Start: 1078
• Page End: 1083
• Publication Date: 2016-11-01
• Subjects: exonuclease -- guide RNA -- mitochondria -- RNA decay -- RNA editing -- Trypanosoma -- TUTase -- uridylation; RNA -- Periodicals; Molecular biology -- Periodicals; Molecular biology; RNA; Periodicals; 572.8805
• DOI: 10.1080/15476286.2016.1229736
• Languages: English
• ISSNs: 1547-6286

Abstract

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.