Deadenylation-independent stage-specific mRNA degradation in Leishmania

Haile, Simon; Dupé, Aurélien; Papadopoulou, Barbara

doi:10.1093/nar/gkn019

Cited by 31 publications

(35 citation statements)

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“…In contrast, depletion of CAF1 (Schwede et al 2008(Schwede et al , 2009 or CNOT10 (Färber et al 2013) affected all mRNAs examined. Detailed studies of EP mRNA degradation kinetics provided clear evidence for a very rapid, deadenylation-independent, and XRNA-dependent 5 ′ -3 ′ pathway, combined with a slower deadenylation-dependent component (Irmer and Clayton 2001;Haile et al 2008;Schwede et al 2009). In the related Kinetoplastid parasite Leishmania there is also evidence for this type of biphasic degradation (Haile et al 2008), and some developmentally unstable mRNAs are subject to endonuclease cleavage in the 3 ′ UTR (Muller et al 2010).…”

Section: Introductionmentioning

confidence: 99%

The roles of 3′-exoribonucleases and the exosome in trypanosome mRNA degradation

Fadda

Färber

Droll

et al. 2013

RNA

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The degradation of eukaryotic mRNAs can be initiated by deadenylation, decapping, or endonuclease cleavage. This is followed by 5 ′ -3 ′ degradation by homologs of Xrn1, and/or 3 ′ -5 ′ degradation by the exosome. We previously reported that, in African trypanosome Trypanosoma brucei, most mRNAs are deadenylated prior to degradation, and that depletion of the major 5 ′ -3 ′ exoribonuclease XRNA preferentially stabilizes unstable mRNAs. We now show that depletion of either CAF1 or CNOT10, two components of the principal deadenylation complex, strongly inhibits degradation of most mRNAs. RNAi targeting another deadenylase, PAN2, or RRP45, a core component of the exosome, preferentially stabilized mRNAs with intermediate half-lives. RRP45 depletion resulted in a 5 ′ bias of mRNA sequences, suggesting action by a distributive 3 ′ -5 ′ exoribonuclease. Results suggested that the exosome is involved in the processing of trypanosome snoRNAs. There was no correlation between effects on half-lives and on mRNA abundance.

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Section: Introductionmentioning

confidence: 99%

The roles of 3′-exoribonucleases and the exosome in trypanosome mRNA degradation

Fadda

Färber

Droll

et al. 2013

RNA

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“…Sinefungin was added 5 min prior to ActD (Li et al 2006;Haile et al 2008). Total RNA was isolated at desired time points and analyzed by Northern blotting.…”

Section: Mrna Half-lives and Protein Synthesis Inhibitionmentioning

confidence: 99%

“…In addition, gene expression has been shown to change dramatically throughout the complex life cycles of these parasites (Haile and Papadopoulou 2007;Rochette et al 2008;Nilsson et al 2010;Siegel et al 2010). Regulation of mRNA decay rates through interactions of RNA-binding proteins (RBPs) with cis-acting sequences in 3 ′ UTRs of trypanosomatid transcripts is central in determining the fate of mRNAs and thus fine-tuning developmental gene expression (McNicoll et al 2005;Bringaud et al 2007;Haile and Papadopoulou 2007;Haile et al 2008;Müller et al 2010b;Kramer 2012;Clayton 2013). Several RBPs, such as zinc finger proteins, Alba-domain proteins, and Pumilio (PUF) proteins, have been found to regulate mRNA stability in trypanosomatids (Clayton 2013;Dupé et al 2014).…”

Section: Introductionmentioning

confidence: 99%

The Pumilio-domain protein PUF6 contributes to SIDER2 retroposon-mediated mRNA decay in Leishmania

Azizi

Dumas

Papadopoulou

2017

RNA

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Leishmania and other trypanosomatid protozoa lack control at the level of transcription initiation and regulate gene expression exclusively post-transcriptionally. We have reported previously that Leishmania harbors a unique class of short interspersed degenerate retroposons (SIDERs) that are predominantly located within 3 ′ ′ ′ ′ ′ UTRs and play a major role in post-transcriptional control. We have shown that members of the SIDER2 subfamily initiate mRNA decay through endonucleolytic cleavage within the second conserved 79-nt signature sequence of SIDER2 retroposons. Here, we have developed an optimized MS2 coat protein tethering system to capture trans-acting factor(s) regulating SIDER2-mediated mRNA decay. Tethering of the MS2 coat protein to a reporter RNA harboring two MS2 stem-loop aptamers and the cognate SIDER2-containing 3 ′ ′ ′ ′ ′ UTR in combination with immunoprecipitation and mass spectrometry analysis led to the identification of RNA-binding proteins with known functions in mRNA decay. Among the candidate SIDER2-interacting proteins that were individually tethered to a SIDER2 reporter RNA, the Pumilio-domain protein PUF6 was shown to enhance degradation and reduce transcript half-life. Furthermore, we showed that PUF6 binds to SIDER2 sequences that include the regulatory 79-nt signature motif, hence contributing to the mRNA decay process. Consistent with a role of PUF6 in SIDER2-mediated decay, genetic inactivation of PUF6 resulted in increased accumulation and higher stability of endogenous SIDER2-bearing transcripts. Overall, these studies provide new insights into regulated mRNA decay pathways in Leishmania controlled by SIDER2 retroposons and propose a broader role for PUF proteins in mRNA decay within the eukaryotic kingdom.

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“…Quite useful for gene function studies are the reporter genes, e.g. luciferase or GFP (green fluorescent protein), which are applicable to studying regulatory elements involved in mRNA stability or initiation of translation control [89][90][91] and to evaluate protein interactions or subcellular distribution.…”

Section: Forward and Reverse Geneticsmentioning

confidence: 99%

Using Genomic Information to Understand Leishmania Biology

Toledo¹

2010

TOPARAJ

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Abstract:The genomes of different species of Leishmania have been deciphered in recent years. We learned that the genome content and organization of Leishmania major, Leishmania braziliensis and Leishmania infantum are highly similar and annotation of these genomes revealed that there are few species-specific genes. Association of genome information with reverse and forward genetics approaches allows posing and answering relevant biological questions in a novel way. In this article we briefly present an overview of relevant aspects of genome organization of the Leishmania and how this information can be used to improve our understanding of the biology, pathogenesis, host-parasite interaction issues. We present some of the most useful bioinformatics tools/softwares, which are currently available and how each one of them can be used to explore the genome supporting a wide variety of queries. We included other computational tools which allow integrating the genome data with biochemical pathways revealing metabolic and regulatory networks to be investigated. Finally, we discuss reverse and forward genetic tools available and finalize with considerations on established and novel high-throughput approaches at the genome, transcriptome and proteome levels.

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Deadenylation-independent stage-specific mRNA degradation in Leishmania

Cited by 31 publications

References 61 publications

The roles of 3′-exoribonucleases and the exosome in trypanosome mRNA degradation

The roles of 3′-exoribonucleases and the exosome in trypanosome mRNA degradation

The Pumilio-domain protein PUF6 contributes to SIDER2 retroposon-mediated mRNA decay in Leishmania

Using Genomic Information to Understand Leishmania Biology

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