Processing the message: structural insights into capping and decapping mRNA

Gu, Meigang; Lima, Christopher D.

doi:10.1016/j.sbi.2005.01.009

Cited by 93 publications

(83 citation statements)

References 35 publications

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“…Saccharomyces cerevisiae RNA 5ʹ-triphosphatease (Cet1p) is a member of the divalent cation-dependent triphosphatase family observed in protozoa, eukaryotic viruses and fungi. [4][5][6][7] The X-ray structure of Cet1p revealed the location of two independent active sites within parallel tunnels that are formed by homodimerization of a domain. 5 In yeast such as S. cerevisiae and Candida albicans, the triphosphatase and guanylyltransferase are encoded by distinct genes whose protein products form a noncovalent complex.…”

Section: Candidiasis Is a Fungal Infection Caused By Yeasts Of The Gementioning

confidence: 99%

Kribellosides, novel RNA 5′-triphosphatase inhibitors from the rare actinomycete Kribbella sp. MI481-42F6

et al. 2017

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Yeast capping enzymes differ greatly from those of mammalian, both structurally and mechanistically. Yeast-type capping enzyme repressors are therefore candidate antifungal drugs. The 5ʹ-guanine-N7 cap structure of mRNAs are an essential feature of all eukaryotic organisms examined to date and is the first co-transcriptional modification of cellular pre-messenger RNA. Inhibitors of the RNA 5ʹ-triphosphatase in yeast are likely to show fungicidal effects against pathogenic yeast such as Candida. We discovered a new RNA 5ʹ-triphosphatase inhibitor, designated as the kribellosides, by screening metabolites from actinomycetes. Kribellosides belong to the alkyl glyceryl ethers. These novel compounds inhibit the activity of Cet1p (RNA 5ʹ-triphosphatase) from Saccharomyces cerevisiae in vitro with IC 50 s of 5-8 μM and show antifungal activity with MICs ranging from 3.12 to 100 μg ml À1 against S. cerevisiae.

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Section: Candidiasis Is a Fungal Infection Caused By Yeasts Of The Gementioning

confidence: 99%

Kribellosides, novel RNA 5′-triphosphatase inhibitors from the rare actinomycete Kribbella sp. MI481-42F6

et al. 2017

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“…However, the specific and regulated cleavage of mRNAs described within this study (see above) appears to produce distinct long 59-capped RNA transcripts that retain, albeit truncated, coding potential, in a manner similar to the recently reported case of the DUX4 gene (Snider et al 2009). Indeed, the secondary 59 capping of such cleaved transcripts may permit their correct localization and translation (Gu and Lima 2005), raising the possibility that a major role of RNA cleavage is to generate alternative mRNA isoforms.…”

Section: Post-transcriptional Cleavage Generates a Diversity Of Long mentioning

confidence: 99%

Regulated post-transcriptional RNA cleavage diversifies the eukaryotic transcriptome

Mercer¹,

Dinger²,

Bracken³

et al. 2010

Genome Res.

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The complexity of the eukaryotic transcriptome is generated by the interplay of transcription initiation, termination, alternative splicing, and other forms of post-transcriptional modification. It was recently shown that RNA transcripts may also undergo cleavage and secondary 59 capping. Here, we show that post-transcriptional cleavage of RNA contributes to the diversification of the transcriptome by generating a range of small RNAs and long coding and noncoding RNAs. Using genomewide histone modification and RNA polymerase II occupancy data, we confirm that the vast majority of intraexonic CAGE tags are derived from post-transcriptional processing. By comparing exonic CAGE tags to tissue-matched PARE data, we show that the cleavage and subsequent secondary capping is regulated in a developmental-stage-and tissue-specific manner. Furthermore, we find evidence of prevalent RNA cleavage in numerous transcriptomic data sets, including SAGE, cDNA, small RNA libraries, and deep-sequenced size-fractionated pools of RNA. These cleavage products include mRNA variants that retain the potential to be translated into shortened functional protein isoforms. We conclude that post-transcriptional RNA cleavage is a key mechanism that expands the functional repertoire and scope for regulatory control of the eukaryotic transcriptome.

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“…Therefore, similar to other proteins that utilize a conventional NLS, human DcpS relies on a region of basic amino acids located in the N-terminal domain of the protein for nuclear protein import. Interestingly, the basic NLS and hydrophobic-rich NES of the scavenger decapping protein are conserved exclusively in human and mouse (Gu and Lima 2005). The cytoplasmic C. elegans DcpS homolog Dcs-1 (Lall et al 2005) and S. cerevisiae DcpS homolog Dcs1 (Malys and McCarthy 2006), lack the first 30 and 31 amino acids, respectively, corresponding to human DcpS, which includes the NLS.…”

Section: Dcps Contains a Basic Region Nuclear Localization Signal (Nls)mentioning

confidence: 99%

“…In the case of the catalytically inactive S. cerevisiae Dcs2, the NLS region is not conserved, and we are unable to decipher another putative NLS (data not shown). The S. pombe homolog of DcpS, Nhm1, is predominantly nuclear but also present in the cytoplasm (Salehi et al 2002); however, neither an NLS nor NES could be readily discerned based on examination of the amino acid sequence (Gu and Lima 2005).…”

Section: Dcps Contains a Basic Region Nuclear Localization Signal (Nls)mentioning

confidence: 99%

DcpS scavenger decapping enzyme can modulate pre-mRNA splicing

Shen¹,

Liu²,

Liu³

et al. 2008

RNA

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The human scavenger decapping enzyme, DcpS, functions to hydrolyze the resulting cap structure following cytoplasmic mRNA decay yet is, surprisingly, a nuclear protein by immunofluorescence. Here, we show that DcpS is a nucleocytoplasmic shuttling protein that contains separable nuclear import and Crm-1-dependent export signals. We postulated that the presence of DcpS in both cellular compartments and its ability to hydrolyze cap structure may impact other cellular events dependent on capbinding proteins. An shRNA-engineered cell line with markedly diminished DcpS levels led to a corresponding reduction in capproximal intron splicing of a reporter minigene and endogenous genes. The impaired cap catabolism and resultant imbalanced cap concentrations were postulated to sequester the cap-binding complex (CBC) from its normal splicing function. In support of this explanation, DcpS efficiently displaced the nuclear cap-binding protein Cbp20 from cap structure, and complementation with Cbp20 reversed the reduced splicing, indicating that modulation of splicing by DcpS is mediated through Cbp20. Our studies demonstrate that the significance of DcpS extends beyond its well-characterized role in mRNA decay and involves a broader range of functions in RNA processing including nuclear pre-mRNA splicing.

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Processing the message: structural insights into capping and decapping mRNA

Cited by 93 publications

References 35 publications

Kribellosides, novel RNA 5′-triphosphatase inhibitors from the rare actinomycete Kribbella sp. MI481-42F6

Kribellosides, novel RNA 5′-triphosphatase inhibitors from the rare actinomycete Kribbella sp. MI481-42F6

Regulated post-transcriptional RNA cleavage diversifies the eukaryotic transcriptome

DcpS scavenger decapping enzyme can modulate pre-mRNA splicing

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