DNA template effect on RNA splicing: two copies of the same gene in the same nucleus are processed differently.

Adami, Guy R.; Babiss, Lee E.

doi:10.1002/j.1460-2075.1991.tb04910.x

Cited by 35 publications

(26 citation statements)

References 52 publications

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“…Consistent with this, NM22 coimmunoprecipitated a higher level of B3-reactive pol IIo compared with NM4 (compare lanes 6 and 7), corresponding to a40-50% of that present in the total extract (compare lanes 4 and 7). Immunoprecipitation of B3-reactive pol IIo by these mAbs appeared to occur through the recognition of SR proteins and not by direct binding to pol IIo, as neither NM22 nor NM4 were reactive with pol IIo in the preparation of purified polymerase (data not shown (31,32). This model is similar to a previous proposal (33) and is also supported by the recent identification of four novel proteins containing SR domains that interact with the CTD of pol 11 (34).…”

Section: Resultssupporting

confidence: 81%

A hyperphosphorylated form of the large subunit of RNA polymerase II is associated with splicing complexes and the nuclear matrix.

Mortillaro

Blencowe

Wei

et al. 1996

Proc. Natl. Acad. Sci. U.S.A.

299

223

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A hyperphosphorylated form of the largest subunit of RNA polymerase II (pol IIo) is associated with the pre-mRNA splicing process. Pol IIo was detected in association with a subset of small nuclear ribonucleoprotein particle and Ser-Arg protein splicing factors and also with pre-mRNA splicing complexes assembled in vitro. A subpopulation of pol hIo was localized to nuclear "speckle" domains enriched in splicing factors, indicating that it may also be associated with RNA processing in vivo. Moreover, pol IIo was retained in a similar pattern following in situ extraction of cells and was quantitatively recovered in the nuclear matrix fraction. The results implicate nuclear matrix-associated hyperphosphorylated pol IIo as a possible link in the coordination of transcription and splicing processes.with pre-mRNA processing that are related to the SR family.In the present study, a new anti-NM mAb, B3, is characterized that recognizes a 250-kDa NM protein concentrated in speckles. Similar to anti-NM mAbs which recognize SR proteins, B3 preferentially binds in vitro to a subset of splicing complexes containing exon sequences. Surprisingly, the B3 antigen corresponds to a hyperphosphorylated form of the large subunit of pol II (pol IIo). In addition to splicing complexes, pol IIo is associated with a subset of snRNP and SR protein splicing factors. The possible implications of these findings in relation to the regulation of RNA processing are discussed. MATERIALS AND METHODSIncreasing evidence suggests that transcription and processing of RNA polymerase II (pol II) transcripts are temporally and spatially linked. Visualization of chromatin spreads by electron microscopy has revealed that the majority of introns are removed cotranscriptionally from pre-mRNA (1, 2). These studies are supported by recent fluorescent in situ hybridization experiments, indicating that the synthesis and splicing of specific pol II transcripts are coincident at discrete foci (3-5).In several cases, transcript foci appear to be localized in association with specific nuclear domains that are highly enriched in splicing factors, referred to as "speckles" (3, 5-7).Although not mutually exclusive with evidence implicating speckle domains in splicing factor storage and/or assembly (8, 9), these transcript localization experiments indicate a possible direct role of speckle domains in the processing of pre-mRNAs (10, 11). Mammalian nuclei typically contain 20-50 speckle domains, which, in addition to the four spliceosomal small nuclear ribonucleoprotein particles (snRNPs; Ul, U2, U4/6, and U5), are also enriched for non-snRNP splicing factors and poly(A)+ RNA (8, 9, 11). Many of the non-snRNP splicing factors in speckles are related to the Ser-Arg (SR) family of proteins, all of which contain one or more domains rich in alternating serine and arginine residues (12). Besides splicing components, speckle structures also contain elevated concentrations of proteins involved in transcription and cellular transformation (13-15). Since these structure...

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Section: Resultssupporting

confidence: 81%

A hyperphosphorylated form of the large subunit of RNA polymerase II is associated with splicing complexes and the nuclear matrix.

Mortillaro

Blencowe

Wei

et al. 1996

Proc. Natl. Acad. Sci. U.S.A.

299

223

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“…In contrast, previous reports presented evidence for a direct effect of the SV40 replication origin in activating the SV40 late promoter (23). Results from adenoviruses (24,25) indicated cis-acting template effects on transcriptional control and posttranscriptional processing. A systematic study of a cis effect of DNA replication on polyoma late gene activation has not yet been reported.…”

mentioning

confidence: 62%

“…As DNA replication has been suggested to influence the gene expression of several animal viruses in cis (17,(23)(24)(25), we carried out cotransfection experiments with wild-type virus and a marked replication-incompetent genome, oriA-M (Fig. 2).…”

Section: Methodsmentioning

confidence: 99%

Polyoma virus early-late switch: regulation of late RNA accumulation by DNA replication.

Liu

Carmichael

1993

Proc. Natl. Acad. Sci. U.S.A.

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Early in infection of permissive mouse cells, messages from the early region of the polyoma virus genome accumulate preferentially over those from the late region. After initiation of DNA replication, the balance between early and late gene expression is reversed in favor of the late products. In previous work from our laboratory, we showed that viral early proteins do not activate the polyoma late promoter in the absence ofDNA replication. Here The molecular details underlying the early-late switch are poorly understood, although large TAg is known to play a pivotal role. Large TAg binds to its target DNA sequences within and adjacent to the replication origin (6-8) and is required for initiation and maintenance of polyoma virus replication. Previous experiments by others suggest that large TAg also transactivates the late promoter and represses transcriptional activity of early genes (2, 9-11). More recent data have suggested an additional involvement of middle TAg in regulating the early-late switch by interacting with host signal transduction pathways, which in turn modify transcription factors (10, 12). However, posttranscriptional regulation may play a more important role than large TAg in accumulation of late messages after DNA replication is initiated (3,(13)(14)(15)(16). Activation of polyoma virus late genes is replicationdependent because (i) polyoma mutants carrying temperature-sensitive large TAg mutations cannot proceed into the late phase at a nonpermissive temperature (2); (ii) cytosine arabinoside (araC), a DNA replication inhibitor, prevents the polyoma virus early-late switch (3,14); and (iii) polyoma virus late genes are generally not expressed in significantThe publication costs of this article were defrayed in part by page charge payment. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. §1734 solely to indicate this fact. levels in transformed nonpermissive cells, in which polyoma fails to replicate (15). Regulation of gene expression by DNA replication could be achieved via trans-or cis-acting mechanisms. Trans-acting factors may be modified, induced, or titrated as a result ofDNA replication. Alternatively, changes in chromatin structure induced by replication may exert a direct cis effect on late gene expression (17, 18). In simian virus 40 (SV40), late genes can be activated in trans by large TAg in the absence of DNA replication (19)(20)(21)(22). Recently, a trans effect involving depletion of an important transcriptional factor has been suggested for polyoma virus late gene activation (12). In contrast, previous reports presented evidence for a direct effect of the SV40 replication origin in activating the SV40 late promoter (23). Results from adenoviruses (24, 25) indicated cis-acting template effects on transcriptional control and posttranscriptional processing. A systematic study of a cis effect of DNA replication on polyoma late gene activation has not yet been reported.We show here that TAg expression in the absence of DNA replic...

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“…It has also been suggested that nuclear compartmentalization is an epigenetic mechanism (Riggs and Porter 1996), and, therefore, the epigenetic factors may play a role in the further processing of mRNAs. At least two experimental studies suggested the role of DNA template-based (cis) factors but not cytoplasmatic (trans) factors in alternative splicing (Adami andBabiss 1991, Hayward et al 1998). The first study demonstrated that different spliced versions of the E1B gene may originate from late and early adenoviral genomes which co-existed in the same cell.…”

Section: Epigenetic Interpretation Of the Drd3 Findings In Sczmentioning

confidence: 99%

The Genes for Major Psychosis Aberrant Sequence or Regulation?

Petronis

2000

Neuropsychopharmacology

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DNA template effect on RNA splicing: two copies of the same gene in the same nucleus are processed differently.

Cited by 35 publications

References 52 publications

A hyperphosphorylated form of the large subunit of RNA polymerase II is associated with splicing complexes and the nuclear matrix.

A hyperphosphorylated form of the large subunit of RNA polymerase II is associated with splicing complexes and the nuclear matrix.

Polyoma virus early-late switch: regulation of late RNA accumulation by DNA replication.

The Genes for Major Psychosis Aberrant Sequence or Regulation?

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