Exaptive origins of regulated mRNA decay in eukaryotes

Hamid, Fursham; Makeyev, Eugene V.

doi:10.1002/bies.201600100

Cited by 13 publications

(14 citation statements)

References 119 publications

(184 reference statements)

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“…In conclusion, we find that terminal uridylyltransferases are potent antiviral factors during the early stages of RNA virus infections in C. elegans and in mammalian cells. This finding supports a scenario where eukaryotic mRNA decay pathways originally evolved as intrinsic cellular defenses against pathogens 32,33 . Terminal uridylyltransferases are widely conserved in eukaryotes and could potentially target a wide range of RNA viruses 30 .…”

Section: Animals With Intestinal Expression Of Cde-1 Became Resistantsupporting

confidence: 82%

Terminal uridylyltransferases target RNA viruses as part of the innate immune system in animals

Pen

Jiang

et al. 2017

Preprint

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terminal uridylation of viral RNAs as a third antiviral mechanism in animals (Extended Data Fig. 1).. CC-BY-NC 4.0 International license peer-reviewed) is the author/funder. It is made available under a The copyright holder for this preprint (which was not . http://dx.doi.org/10.1101/209114 doi: bioRxiv preprint first posted online Oct. 25, 2017; Le Pen et al., page 3 of 51We carried out a forward genetic screen to discover antiviral pathways in animals using the nematode Caenorhabditis elegans and its natural intestinal pathogen, the Orsay virus (OrV) [4][5][6][7][8][9][10][11][12] (Extended Data Fig. 1). While C. elegans lacks an interferon pathway, a RIG-I ortholog, DRH-1, acts in viral recognition. DRH-1 forms a Viral Recognition Complex (ViRC) with the C. elegans Dicer (DCR-1) and the RNA-binding protein RDE-4 to link viral recognition to a dedicated antiviral RNAi pathway 5,11,13,14 (Extended Data Fig. 1). DRH-1 also induces a transcriptional immune response through an as yet uncharacterized signaling pathway 10,15 . We generated a viral stress sensor transgene by placing the green fluorescent protein (GFP) under the control of the lys-3 promoter (allele mjIs228), an immune response gene ( Fig. 1a and Extended Data Fig. 2a).Upon infection, the level of GFP expression in the intestine mirrored the viral load in wild type, Fig. 2b, c). We used chemical mutagenesis to screen ~50,000 haploid genomes ( Fig. 1b) and identified 16 isolates we named Ovid (Orsay Virus Immune Deficient; Fig. 1c and Extended Data Table 1). 13 out of 16 ovid mutants showed increased viral loads 4,5,10,12 are compromised in somatic RNAi 4,10 carry new alleles of RNAi genes mut-16, rde-4 and rrf-1, respectively (Table 1). To further stratify our Ovid isolates, we assayed DRH-1 pathway activation using the expression of a downstream induced gene named sdz-6 as readout 10 ( Fig. 1d and Extended Data Fig. 2a). Only ovid-1 phenocopied drh-1 mutants, defining a new allele of drh-1 (Fig. 1d). We identified a number of additional candidate genes (Table 1). ovid-9 and ovid-11 mutants are neither defective in canonical RNAi nor in the DRH-1 pathway and thus represent candidate genes for novel antiviral defense mechanisms. drh-1 and rde-1 mutants (Extended Data. CC-BY-NC 4.0 International license peer-reviewed) is the author/funder. It is made available under a The copyright holder for this preprint (which was not . http://dx.doi.org/10.1101/209114 doi: bioRxiv preprint first posted online Oct. 25, 2017; Le Pen et al., page 4 of 51 Whole-genome re-sequencing and genetic complementation tests revealed the causative mutation in ovid-9 to be a single-nucleotide nonsense mutation in the cde-1 gene (mj414, glutamine 910 to STOP) ( Fig. 2a and Extended Data Fig. 3). cde-1 encodes a catalytically active 3ʹ-terminal RNA uridylyltransferase (TUT), which is a homologue of mammalian TUT4 and TUT7 enzymes [16][17][18] ( Fig. 2a). The independently derived cde-1 (tm1021) knockout strain also phenocopied viral stress sensor activation (Extended Data Fi...

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Section: Animals With Intestinal Expression Of Cde-1 Became Resistantsupporting

confidence: 82%

Terminal uridylyltransferases target RNA viruses as part of the innate immune system in animals

Pen

Jiang

et al. 2017

Preprint

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“…In this issue of BioEssays , Hamid and Makeyev explore an interesting new idea regarding the evolutionary origins of regulated mRNA turnover pathways . One such pathway is nonsense‐mediated decay (NMD) that detects and targets for degradation a subset of mRNAs including transcripts with premature translation termination codons.…”

mentioning

confidence: 99%

“…NMD recognizes unusual patterns of mRNA translation, particularly atypical positions of stop codons. This feature is shared by some viral mRNAs as a result of the compact genome structure of many viruses and predisposes them to NMD . Another example for regulated mRNA decay that also targets viral RNAs is a group of RNA‐binding proteins containing Zn‐fingers that destabilize specific mRNAs.…”

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confidence: 99%

Is anti‐viral defence the evolutionary origin of mRNA turnover? (Comment on DOI 10.1002/bies.201600100)

Rehwinkel

2016

BioEssays

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“…The author should also mention a recent paper in yeast describing that poor translation efficiency is a major criteria for NMD targeting (Celik et al, 2017 2 ). This major result could potentially explain not yet understood deregulations observed in several other species upon NMD knockdown.It was proposed that invading RNAs of external origin, including TEs and viruses, could be a driving force for NMD apparition and evolution - this should be mentioned in the paragraph on the possible origin of NMD (Hamid and Makeyev, 2016 3 ). …”

mentioning

confidence: 99%

“…It was proposed that invading RNAs of external origin, including TEs and viruses, could be a driving force for NMD apparition and evolution - this should be mentioned in the paragraph on the possible origin of NMD (Hamid and Makeyev, 2016 3 ).…”

mentioning

confidence: 99%

The evolution and diversity of the nonsense-mediated mRNA decay pathway

Lloyd¹

2018

F1000Res

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Nonsense-mediated mRNA decay is a eukaryotic pathway that degrades transcripts with premature termination codons (PTCs). In most eukaryotes, thousands of transcripts are degraded by NMD, including many important regulators of development and stress response pathways. Transcripts can be targeted to NMD by the presence of an upstream ORF or by introduction of a PTC through alternative splicing. Many factors involved in the recognition of PTCs and the destruction of NMD targets have been characterized. While some are highly conserved, others have been repeatedly lost in eukaryotic lineages. Here, I outline the factors involved in NMD, our current understanding of their interactions and how they have evolved. I outline a classification system to describe NMD pathways based on the presence/absence of key NMD factors. These types of NMD pathways exist in multiple different lineages, indicating the plasticity of the NMD pathway through recurrent losses of NMD factors during eukaryotic evolution. By classifying the NMD pathways in this way, gaps in our understanding are revealed, even within well studied organisms. Finally, I discuss the likely driving force behind the origins of the NMD pathway before the appearance of the last eukaryotic common ancestor: transposable element expansion and the consequential origin of introns.

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Exaptive origins of regulated mRNA decay in eukaryotes

Cited by 13 publications

References 119 publications

Terminal uridylyltransferases target RNA viruses as part of the innate immune system in animals

Terminal uridylyltransferases target RNA viruses as part of the innate immune system in animals

Is anti‐viral defence the evolutionary origin of mRNA turnover? (Comment on DOI 10.1002/bies.201600100)

The evolution and diversity of the nonsense-mediated mRNA decay pathway

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