Methylated, blocked 5 termini in HeLa cell mRNA.

Furuichi, Yasuhiro; Morgan, M.; Shatkin, Aaron J.; Jelinek, Warren R.; Salditt-Georgieff, M; Darnell, James

doi:10.1073/pnas.72.5.1904

Cited by 242 publications

(239 citation statements)

References 13 publications

Supporting

Mentioning

227

Contrasting

Order By: Relevance

“…That same structure was soon found also in both cellular nuclear RNA and polyribosomal mRNA (Perry and Kelley 1974;Furuichi et al 1975b;Wei et al 1975;Salditt-Georgieff et al 1976). …”

Section: Polya-first Strong Indication Of Pre-mrna Processingmentioning

confidence: 72%

Reflections on the history of pre-mRNA processing and highlights of current knowledge: A unified picture

Darnell¹

2013

RNA

View full text Add to dashboard Cite

Several strong conclusions emerge concerning pre-mRNA processing from both old and newer experiments. The RNAPII complex is involved with pre-mRNA processing through binding of processing proteins to the CTD (carboxyl terminal domain) of the largest RNAPII subunit. These interactions are necessary for efficient processing, but whether factor binding to the CTD and delivery to splicing sites is obligatory or facilitatory is unsettled. Capping, addition of an m 7 Gppp residue (cap) to the initial transcribed residue of a pre-mRNA, occurs within seconds. Splicing of pre-mRNA by spliceosomes at particular sites is most likely committed during transcription by the binding of initiating processing factors and ∼50% of the time is completed in mammalian cells before completion of the primary transcript. This fact has led to an outpouring in the literature about "cotranscriptional splicing." However splicing requires several minutes for completion and can take longer. The RNAPII complex moves through very long introns and also through regions dense with alternating exons and introns at an average rate of ∼3 kb per min and is, therefore, not likely detained at each splice site for more than a few seconds, if at all. Cleavage of the primary transcript at the 3 ′ end and polyadenylation occurs within 30 sec or less at recognized polyA sites, and the majority of newly polyadenylated pre-mRNA molecules are much larger than the average mRNA. Finally, it seems quite likely that the nascent RNA most often remains associated with the chromosomal locus being transcribed until processing is complete, possibly acquiring factors related to the transport of the new mRNA to the cytoplasm.

show abstract

“…That same structure was soon found also in both cellular nuclear RNA and polyribosomal mRNA (Perry and Kelley 1974;Furuichi et al 1975b;Wei et al 1975;Salditt-Georgieff et al 1976). …”

Section: Polya-first Strong Indication Of Pre-mrna Processingmentioning

confidence: 72%

Reflections on the history of pre-mRNA processing and highlights of current knowledge: A unified picture

Darnell¹

2013

RNA

View full text Add to dashboard Cite

show abstract

“…One possible modification between the first and second bases of an mRNA would be a 29-O-methylation of the sugar attached to the first templated base of the splice leader. This modification has been observed in other systems (e.g., Furuichi et al 1975) and would certainly be expected to influence the rate of alkali cleavage.…”

Section: Resultsmentioning

confidence: 93%

Multimodal RNA-seq using single-strand, double-strand, and CircLigase-based capture yields a refined and extended description of the C. elegans transcriptome

Lamm¹,

Stadler²,

Zhang³

et al. 2010

Genome Res.

View full text Add to dashboard Cite

We have used a combination of three high-throughput RNA capture and sequencing methods to refine and augment the transcriptome map of a well-studied genetic model, Caenorhabditis elegans. The three methods include a standard (non-directional) library preparation protocol relying on cDNA priming and foldback that has been used in several previous studies for transcriptome characterization in this species, and two directional protocols, one involving direct capture of single-stranded RNA fragments and one involving circular-template PCR (CircLigase). We find that each RNA-seq approach shows specific limitations and biases, with the application of multiple methods providing a more complete map than was obtained from any single method. Of particular note in the analysis were substantial advantages of CircLigase-based and ssRNA-based capture for defining sequences and structures of the precise 59 ends (which were lost using the double-strand cDNA capture method). Of the three methods, ssRNA capture was most effective in defining sequences to the poly(A) junction. Using data sets from a spectrum of C. elegans strains and stages and the UCSC Genome Browser, we provide a series of tools, which facilitate rapid visualization and assignment of gene structures.

show abstract

“…The presence of a 5= cap structure m 7 G(5=)ppp(5=)Nm is a general feature of eukaryotic mRNAs and many viral mRNAs that provides protection from exonuclease digestion and enhances translation (1)(2)(3)(4)(5)(6). In eukaryotic cells, mRNA decay begins with shortening of the poly(A) tail and proceeds in either the 5=-to-3= or 3=-to-5= direction.…”

mentioning

confidence: 99%

The D10 Decapping Enzyme of Vaccinia Virus Contributes to Decay of Cellular and Viral mRNAs and to Virulence in Mice

Liu

Wyatt

Orandle

et al. 2014

J Virol

View full text Add to dashboard Cite

bPosttranscriptional mechanisms are important for regulation of cellular and viral gene expression. The presence of the 5= cap structure m 7 G(5=)ppp(5=)Nm is a general feature of mRNAs that provides protection from exoribonuclease digestion and enhances translation. Vaccinia virus and other poxviruses encode enzymes for both cap synthesis and decapping. Decapping is mediated by two related enzymes, D9 and D10, which are synthesized before and after viral DNA replication, respectively. The timing of D10 synthesis correlates better with the shutdown of host gene expression, and deletion of this gene has been shown to cause persistence of host and viral mRNAs in infected cells. Here, we constructed specific mutant viruses in which translation of D10 was prevented by stop codons or activity of D10 was abrogated by catalytic site mutations, without other genomic alterations. Both mutants formed plaques of normal size and replicated to similar extents as the parental virus in monkey epithelial cells and mouse embryonic fibroblasts. The synthesis of viral proteins was slightly delayed, and cellular and viral mRNAs persisted longer in cells infected with the mutants compared to either the parental virus or clonal revertant. Despite the mild effects in vitro, both mutants were more attenuated than the revertants in intranasal and intraperitoneal mouse models, and less infectious virus was recovered from organs. In addition, there was less lung histopathology following intranasal infection with mutant viruses. These data suggest that the D10 decapping enzyme may help restrict antiviral responses by accelerating host mRNA degradation during poxvirus infection. P osttranscriptional mechanisms are important for the regulation of cellular and viral gene expression at the levels of RNA stability and translation. The presence of a 5= cap structure m 7 G(5=)ppp(5=)Nm is a general feature of eukaryotic mRNAs and many viral mRNAs that provides protection from exonuclease digestion and enhances translation (1-6). In eukaryotic cells, mRNA decay begins with shortening of the poly(A) tail and proceeds in either the 5=-to-3= or 3=-to-5= direction. The latter is mediated by the cytoplasmic RNA exosome (7-9) and a scavenger enzyme that degrades the cap (8). In the 5=-to-3= pathway, removal of the cap (10-13) is followed by exoribonuclease Xrn1 digestion (14,15). Enzymes with nudix hydrolase motifs that decap cytoplasmic mRNA are present in Saccharomyces cerevisiae and mammalian cells and are thought to function in mRNA decay (10-13, 16, 17).Degradation of cellular mRNA may be advantageous to viruses by decreasing competition for the translational machinery and by reducing the synthesis of factors that contribute to the innate and adaptive immune responses to infection. The ability of viruses to accelerate mRNA decay has been intensively studied with members of the herpesvirus family, which replicate in the nucleus and utilize the transcriptional machinery of the cell (18, 19). For alphaherpesviruses, accelerated mRNA turnover is mediat...

show abstract

Methylated, blocked 5 termini in HeLa cell mRNA.

Cited by 242 publications

References 13 publications

Reflections on the history of pre-mRNA processing and highlights of current knowledge: A unified picture

Reflections on the history of pre-mRNA processing and highlights of current knowledge: A unified picture

Multimodal RNA-seq using single-strand, double-strand, and CircLigase-based capture yields a refined and extended description of the C. elegans transcriptome

The D10 Decapping Enzyme of Vaccinia Virus Contributes to Decay of Cellular and Viral mRNAs and to Virulence in Mice

Contact Info

Product

Resources

About