title: The role of the 5'-3' exoribonuclease XRNA in transcriptome-wide mRNA degradation.
abstract: The steady-state level of each mRNA in a cell is a balance between synthesis and degradation. Here, we use high-throughput RNA sequencing (RNASeq) to determine the relationship between mRNA degradation and mRNA abundance on a transcriptome-wide scale. The model organism used was the bloodstream form of Trypanosoma brucei, a protist that lacks regulation of RNA polymerase II initiation. The mRNA half-lives varied over two orders of magnitude, with a median half-life of 13 min for total (rRNA-depleted) mRNA. Data for poly(A)+ RNA yielded shorter half-lives than for total RNA, indicating that removal of the poly(A) tail was usually the first step in degradation. Depletion of the major 5'-3' exoribonuclease, XRNA, resulted in the stabilization of most mRNAs with half-lives under 30 min. Thus, on a transcriptome-wide scale, degradation of most mRNAs is initiated by deadenylation. Trypanosome mRNA levels are strongly influenced by gene copy number and mRNA half-life: Very abundant mRNAs that are required throughout the life-cycle may be encoded by multicopy genes and have intermediate-to-long half-lives; those encoding ribosomal proteins, with one to two gene copies, are exceptionally stable. Developmentally regulated transcripts with a lower abundance in the bloodstream forms than the procyclic forms had half-lives around the median, whereas those with a higher abundance in the bloodstream forms than the procyclic forms, such as those encoding glycolytic enzymes, had longer half-lives.
authors.affiliation: Zentrum für Molekulare Biologie der Universität Heidelberg, DKFZ-ZMBH Alliance, D69120 Heidelberg, Germany.
authors.forename: Theresa
authors.initials: T
authors.lastname: Manful
authors.forename: Abeer
authors.initials: A
authors.lastname: Fadda
authors.forename: Christine
authors.initials: C
authors.lastname: Clayton
mesh_terms: D005095:Exoribonucleases / Q000378:metabolism*; D016366:Open Reading Frames; D020871:RNA Stability; D012333:RNA, Messenger / Q000378:metabolism*; D016053:RNA, Protozoan / Q000378:metabolism*; D059467:Transcriptome; D014346:Trypanosoma brucei brucei / Q000201:enzymology* / Q000235:genetics
chemical_list: D012333:RNA, Messenger; D016053:RNA, Protozoan; D005095:Exoribonucleases; C028793:5'-exoribonuclease