Integrating mRNA Processing with Transcription

Proudfoot, Nick J.; Furger, André; Dye, Michael J.

doi:10.1016/s0092-8674(02)00617-7

Cited by 943 publications

(792 citation statements)

References 81 publications

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“…Interestingly, RNPS1 also interacts with the largest subunit of RNA polymerase II. It was shown that the phosphorylation of the CTD of RNA polymerase also plays a role in posttranscriptional mRNA processing (Proudfoot et al, 2002). The RNA polymerase multiprotein complex also harbours cdk11, which is a cyclin-dependent kinase.…”

Section: Discussionmentioning

confidence: 99%

Protein kinase CK2 interacts with the splicing factor hPrp3p

et al. 2007

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Numerous signalling pathways in cells are influenced by the ubiquitous Ser/Thr protein kinase CK2. Protein kinase CK2 is composed of two regulatory b-subunits and two catalytic a-or a 0 -subunits. Several of the known CK2 substrates are proteins known to regulate transcriptional events. Here, we describe that protein kinase CK2 interacts with the splicing factor hPrp3p, which is important for the assembly of the spliceosome. In a twohybrid screen hPrp3p is exclusively bound to the catalytic a-or a 0 -subunits of CK2 but not to the regulatory bsubunit. The interaction was confirmed by coimmunoprecipitation experiments in vitro and in vivo. Moreover, both proteins colocalized in nuclear speckles which is typical for splicing factor compartments within the nucleus. Phosphorylation experiments revealed that hPrp3p is also a substrate of protein kinase CK2. The main phosphorylation site was mapped to C-terminal residues. In vitro and in vivo splicing assays showed that the splicing activity is significantly influenced by the CK2-hPrp3p interaction. Thus, these data showed that CK2 is involved in the regulation of RNA processing.

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Section: Discussionmentioning

confidence: 99%

Protein kinase CK2 interacts with the splicing factor hPrp3p

et al. 2007

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“…However, it is not surprising that increased gene expression occurs with enhanced mRNA processing, since proteins that catalyze polyadenylation are associated with RNA polymerase II (Pol II), providing a link between transcription and formation of the 3 0 end of mRNA (Maniatis and Reed, 2000;Proudfoot et al, 2000). A functional polyadenylation signal terminates transcription and release Pol II (Whale and Ruegsegger, 1999;Shatkin and Manley, 2000), although polyadenylation seems to continue post-transcriptionally (Osheim et al, 1999(Osheim et al, , 2002.…”

Section: Discussionmentioning

confidence: 99%

Retinoid‐dependent mRNA expression and poly‐(A) contents in bovine oocytes meiotically arrested and/or matured in vitro

Gómez

Rodríguez

Dd́ez

et al. 2004

Molecular Reproduction Devel

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The presence of retinoic acid (RA) during in vitro maturation (IVM) improves bovine oocyte quality and developmental potential. In this work, we investigated the underlying molecular mechanisms. Cumulus-oocyte complexes were meiotically arrested by roscovitine and/or matured in defined medium containing RA, 1% ethanol (vehicle), or no additives. Cumulus-free oocytes were analyzed for poly-(A) mRNA contents and relative mRNA expression of genes involved in cell cycle regulation (cyclin B1 and H1) and antioxidative defence (Mn-superoxide dismutase and glucose-6-phosphate dehydrogenase). Poly-(A) mRNA increased after meiotic inhibition and decreased with IVM completion, both in meiotically arrested and permissively matured oocytes, i.e., matured without previous meiotic arrest. RA dramatically increased poly-(A) mRNA in meiotically arrested oocytes, but more than half of the poly-(A) mRNA disappeared during maturation. Irrespective of oocyte origin, transcripts were detected for all the genes analyzed. IVM, with or without previous meiotic inhibition, increased expression of cyclin B1 and glucose-6-phosphate dehydrogenase, and decreased cyclin H1 and Mn-superoxide dismutase. Except for a decreasing of Mn-superoxide dismutase in meiotically arrested and matured oocytes, RA did not affect mRNA expression. Ethanol led to an abnormal poly-(A) mRNA profile and expression of all the genes analyzed. RA does not modify expression of cyclin B1 and HI genes in the bovine oocyte, and probably does not generate oxidative stress. In addition, RA enhanced mRNA amount as measured by poly-(A) mRNA contents.

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“…(19) Many pre-mRNAs are spliced before transcription is completed; this cotranscriptional splicing probably plays an important role in ensuring the accuracy of splicing. In cotranscriptional splicing, the evidence suggests that the splicing machinery is physically associated with the RNA synthesis machinery (RNA polymerase and its associated factors).…”

Section: Why So Many Proteins?mentioning

confidence: 99%

The spliceosome: the most complex macromolecular machine in the cell?

2003

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SummaryThe primary transcripts, pre-mRNAs, of almost all protein-coding genes in higher eukaryotes contain multiple non-coding intervening sequences, introns, which must be precisely removed to yield translatable mRNAs. The process of intron excision, splicing, takes place in a massive ribonucleoprotein complex known as the spliceosome. Extensive studies, both genetic and biochemical, in a variety of systems have revealed that essential components of the spliceosome include five small RNAs-U1, U2, U4, U5 and U6, each of which functions as a RNA, protein complex called an snRNP (small nuclear ribonucleoprotein). In addition to snRNPs, splicing requires many non-snRNP protein factors, the exact nature and number of which has been unclear. Technical advances, including new affinity purification methods and improved mass spectrometry techniques, coupled with the completion of many genome sequences, have now permitted a number of proteomic analyses of purified spliceosomes. These studies, recently reviewed by Jurica and Moore, (1) reveal that the spliceosome is composed of as many as 300 distinct proteins and five RNAs, making it among the most complex macromolecular machines known. The splicing cycleIntrons within pre-mRNAs are bounded by conserved sequences that define their ends, the 5 0 and 3 0 splice sites respectively. Another conserved sequence called the branchpoint region is located within the intron, usually 20-40 nucleotides upstream of the 3 0 splice site; the branchpoint itself is almost always an adenosine. The details of the process whereby introns are recognized by the splicing machinery is still poorly understood; nevertheless, it is clear that the splice sites and branchpoint region interact with specific RNA and protein factors to engage the spliceosome. For many years, it was thought that the spliceosome formed in a stepwise fashion; however, recent evidence suggests that the spliceosome may be largely pre-assembled. (2,3) Upon complete assembly, or engagement, of the intron, the spliceosome undergoes a series of dramatic rearrangements involving both its RNA and protein constituents prior to catalysis. These rearrangements result in the removal of two snRNPs, U1 and U4 snRNPs, and the addition of more protein factors. (4,6) Splicing itself occurs in two steps; in the first, the 2 0 hydroxyl of the branchpoint adenosine attacks the 5 0 splice junction, breaking that phosphodiester bond and simultaneously forming a 2 0 5 0 phosphodiester linkage between the branchpoint and the 5 0 terminal nucleotide of the intron. The products of the first step are thus free 5 0 exon and intron-3 0 exon, with the intron in the form of a lariat. After another conformational change within the spliceosome, the second step takes place. Here, the newly released 3 0 hydroxyl of the 5 0 exon, created by the first step, attacks the 3 0 splice junction, breaking that phosphodiester bond while forming a new phosphodiester bond between the 5 0 exon and 3 0 exon. Accordingly, the products of the second step are ligated exons...

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Integrating mRNA Processing with Transcription

Cited by 943 publications

References 81 publications

Protein kinase CK2 interacts with the splicing factor hPrp3p

Protein kinase CK2 interacts with the splicing factor hPrp3p

Retinoid‐dependent mRNA expression and poly‐(A) contents in bovine oocytes meiotically arrested and/or matured in vitro

The spliceosome: the most complex macromolecular machine in the cell?

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