Poly(A)-Specific Ribonuclease (PARN-1) Function in Stage-Specific mRNA Turnover in Trypanosoma brucei

Department of Microbiology and Molecular Genetics, University of Medicine and Dentistry-New Jersey Medical School, Newark, NJ 07103, USA.
Eukaryotic Cell (Impact Factor: 3.18). 07/2011; 10(9):1230-40. DOI: 10.1128/EC.05097-11
Source: PubMed


Deadenylation is often the rate-limiting event in regulating the turnover of cellular mRNAs in eukaryotes. Removal of the poly(A) tail initiates mRNA degradation by one of several decay pathways, including deadenylation-dependent decapping, followed by 5' to 3' exonuclease decay or 3' to 5' exosome-mediated decay. In trypanosomatids, mRNA degradation is important in controlling the expression of differentially expressed genes. Genomic annotation studies have revealed several potential deadenylases. Poly(A)-specific RNase (PARN) is a key deadenylase involved in regulating gene expression in mammals, Xenopus oocytes, and higher plants. Trypanosomatids possess three different PARN genes, PARN-1, -2, and -3, each of which is expressed at the mRNA level in two life-cycle stages of the human parasite Trypanosoma brucei. Here we show that T. brucei PARN-1 is an active deadenylase. To determine the role of PARN-1 on mRNA stability in vivo, we overexpressed this protein and analyzed perturbations in mRNA steady-state levels as well as mRNA half-life. Interestingly, a subset of mRNAs was affected, including a family of mRNAs that encode stage-specific coat proteins. These data suggest that PARN-1 functions in stage-specific protein production.

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Available from: Vivian Bellofatto, Mar 24, 2015
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    • "Depletion of PAN2 or an essential exosome subunit had minor effects, mostly on mRNAs of intermediate stability. The roles of the PARN proteins are unclear (Utter et al., 2011). "
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    • "The letters in brackets correspond to the reference publications that describe each experiment: a: (23), b: (26), c: (25), d: (21), e: (22). (B) Trypanosoma brucei genes (blue dots) are mapped on the first two principal components of 22 previously published expression data sets (21–27). Local enrichment of motifs was examined in different regions of the expression hyperspace, with each region corresponding to the center of a set of co-regulated genes (see the ‘Materials and Methods’ section). "
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