Biological implications of decapping: beyond bulk mRNA decay

Borbolis, Fivos; Syntichaki, Popi

doi:10.1111/febs.15798

Cited by 27 publications

(20 citation statements)

References 161 publications

(248 reference statements)

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“…40 new proteins were added to the previous collection. Among new proteins that were added in this release are SARS Cov-2 NSP proteins involved in the capping of viral RNA ( 30–32 ) and a collection of decapping enzymes from Nudix, DXO, HIT and APAH-like families ( 33 ). Besides these newly characterized enzymes, data entries for many enzymes and associated pathways were updated.…”

Section: Database Contentmentioning

confidence: 99%

MODOMICS: a database of RNA modification pathways. 2021 update

Boccaletto

Stefaniak

Ray

et al. 2021

Nucleic Acids Research

573

437

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The MODOMICS database has been, since 2006, a manually curated and centralized resource, storing and distributing comprehensive information about modified ribonucleosides. Originally, it only contained data on the chemical structures of modified ribonucleosides, their biosynthetic pathways, the location of modified residues in RNA sequences, and RNA-modifying enzymes. Over the years, prompted by the accumulation of new knowledge and new types of data, it has been updated with new information and functionalities. In this new release, we have created a catalog of RNA modifications linked to human diseases, e.g., due to mutations in genes encoding modification enzymes. MODOMICS has been linked extensively to RCSB Protein Data Bank, and sequences of experimentally determined RNA structures with modified residues have been added. This expansion was accompanied by including nucleotide 5′-monophosphate residues. We redesigned the web interface and upgraded the database backend. In addition, a search engine for chemically similar modified residues has been included that can be queried by SMILES codes or by drawing chemical molecules. Finally, previously available datasets of modified residues, biosynthetic pathways, and RNA-modifying enzymes have been updated. Overall, we provide users with a new, enhanced, and restyled tool for research on RNA modification. MODOMICS is available at https://iimcb.genesilico.pl/modomics/.

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Section: Database Contentmentioning

confidence: 99%

MODOMICS: a database of RNA modification pathways. 2021 update

Boccaletto

Stefaniak

Ray

et al. 2021

Nucleic Acids Research

573

437

View full text Add to dashboard Cite

show abstract

“…In eukaryotic cells, decapping enzymes play a major role in determining mRNA fate, and thus their activity is tightly regulated [15]. The function of the cellular decapping enzyme DCP2, for example, is controlled by both cis-acting factors, such as autoinhibition by its C-terminal domain, and trans-acting proteins that regulate its activity on specific mRNA substrates [16][17][18].…”

Section: Introductionmentioning

confidence: 99%

Vaccinia virus D10 has broad decapping activity that is regulated by mRNA splicing

Burgess

Shah

et al. 2022

PLoS Pathog

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The mRNA 5’ cap structure serves both to protect transcripts from degradation and promote their translation. Cap removal is thus an integral component of mRNA turnover that is carried out by cellular decapping enzymes, whose activity is tightly regulated and coupled to other stages of the mRNA decay pathway. The poxvirus vaccinia virus (VACV) encodes its own decapping enzymes, D9 and D10, that act on cellular and viral mRNA, but may be regulated differently than their cellular counterparts. Here, we evaluated the targeting potential of these viral enzymes using RNA sequencing from cells infected with wild-type and decapping mutant versions of VACV as well as in uninfected cells expressing D10. We found that D9 and D10 target an overlapping subset of viral transcripts but that D10 plays a dominant role in depleting the vast majority of human transcripts, although not in an indiscriminate manner. Unexpectedly, the splicing architecture of a gene influences how robustly its corresponding transcript is targeted by D10, as transcripts derived from intronless genes are less susceptible to enzymatic decapping by D10. As all VACV genes are intronless, preferential decapping of transcripts from intron-containing genes provides an unanticipated mechanism for the virus to disproportionately deplete host transcripts and remodel the infected cell transcriptome.

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“…Dcp2 was the first discovered decapping enzyme from budding yeast Saccharomyces cerevisiae [13], followed by numerous homologs found in other organisms, including humans and plants [4,[14][15][16][17]. The human genome encodes multiple decapping enzymes [18].…”

Section: Introductionmentioning

confidence: 99%

A poxvirus decapping enzyme localizes to mitochondria to regulate RNA metabolism and translation, and promote viral replication

Cao

Molina

Cantu

et al. 2021

Preprint

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Decapping enzymes remove the five-primer cap of eukaryotic mRNA, leading to accelerated RNA decay. They are critical in regulating RNA homeostasis and play essential roles in many cellular and life processes. They are encoded in many organisms and viruses, including vaccinia virus, which was used as the vaccine to eradicate smallpox. Vaccinia virus encodes two decapping enzymes, D9 and D10, that are necessary for efficient viral replication and pathogenesis. However, the underlying molecular mechanism regulating vaccinia decapping enzyme functions is still largely elusive. Here we demonstrated that vaccinia D10 localized almost exclusively to mitochondria that are highly mobile cellular organelles, providing an innovative mechanism to concentrate D10 locally and mobilize it to efficiently decap mRNAs. As mitochondria were barely present in viral factories, where viral transcripts are produced, suggesting that mitochondrial localization provides a spatial mechanism to preferentially decap cellular mRNAs over viral mRNAs. We identified three amino acids responsible for D10 mitochondrial localization. Loss of mitochondrial localization significantly impaired viral replication, reduced D10 ability to resolve RNA five-primer cap aggregation during infection, diminished D10 gene expression shutoff and mRNA translation promotion abilities.

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Biological implications of decapping: beyond bulk mRNA decay

Cited by 27 publications

References 161 publications

MODOMICS: a database of RNA modification pathways. 2021 update

MODOMICS: a database of RNA modification pathways. 2021 update

Vaccinia virus D10 has broad decapping activity that is regulated by mRNA splicing

A poxvirus decapping enzyme localizes to mitochondria to regulate RNA metabolism and translation, and promote viral replication

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