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Co-transcriptional nuclear actin dynamics.

Percipalle P - Nucleus (2012)

Bottom Line: This high degree of promiscuity in the spectrum of protein-to-protein interactions correlates well with the conformational plasticity of actin and the ability to undergo regulated changes in its polymerization states.Several of the factors involved in controlling head-to-tail actin polymerization have been shown to be in the nucleus where they seem to regulate gene activity.By focusing on the multiple tasks performed by actin and actin-binding proteins, possible models of how actin dynamics controls the different phases of the RNA polymerase II transcription cycle are being identified.

View Article: PubMed Central - PubMed

Affiliation: Department of Cell and Molecular Biology, Karolinska Institute, Stockholm, Sweden. piergiorgio.percipalle@ki.se

ABSTRACT
Actin is a key player for nuclear structure and function regulating both chromosome organization and gene activity. In the cell nucleus actin interacts with many different proteins. Among these proteins several studies have identified classical nuclear factors involved in chromatin structure and function, transcription and RNA processing as well as proteins that are normally involved in controlling the actin cytoskeleton. These discoveries have raised the possibility that nuclear actin performs its multi task activities through tight interactions with different sets of proteins. This high degree of promiscuity in the spectrum of protein-to-protein interactions correlates well with the conformational plasticity of actin and the ability to undergo regulated changes in its polymerization states. Several of the factors involved in controlling head-to-tail actin polymerization have been shown to be in the nucleus where they seem to regulate gene activity. By focusing on the multiple tasks performed by actin and actin-binding proteins, possible models of how actin dynamics controls the different phases of the RNA polymerase II transcription cycle are being identified.

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Figure 1. The possible contribution of actin in RNA polymerase II transcription activation. Top panel, monomeric actin interacts with the PSF/NonO complex to recruit the positive elongation factor P-TEFb with the subunit cdk9. This in turn leads to Ser2 phosphorylation within the heptapeptide repeats of the RNA polymerase II CTD. This mechanism promotes RNA polymerase II CTD escape from pausing. Bottom panel, the CTD associated-actin interacts with hnRNP U and this mechanism commits the hyperphosphorylated RNA polymerase II to transcription elongation through recruitment of the HAT PCAF. RNAPII, RNA polymerase II; U, hnRNP U; T, ATP-actin; P-S2, phosphorylated Ser2; P-S5, phosphorylated Ser5.
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Figure 1: Figure 1. The possible contribution of actin in RNA polymerase II transcription activation. Top panel, monomeric actin interacts with the PSF/NonO complex to recruit the positive elongation factor P-TEFb with the subunit cdk9. This in turn leads to Ser2 phosphorylation within the heptapeptide repeats of the RNA polymerase II CTD. This mechanism promotes RNA polymerase II CTD escape from pausing. Bottom panel, the CTD associated-actin interacts with hnRNP U and this mechanism commits the hyperphosphorylated RNA polymerase II to transcription elongation through recruitment of the HAT PCAF. RNAPII, RNA polymerase II; U, hnRNP U; T, ATP-actin; P-S2, phosphorylated Ser2; P-S5, phosphorylated Ser5.

Mentions: Several reports support a role for actin in commitment and maintenance of transcription elongation. The positive elongation factor P-TEFb, required by the RNA polymerase II for escape from pausing, is recruited via polymerase-associated actin, a mechanism that leads to hyperphosphorylation of the CTD and commitment to elongation (Fig. 1).36 To find out how actin actually functions in transcription elongation, nuclear RNP preparations from both C. tentans and mammalian cells were screened by DNase I affinity chromatography to pull-down actin and potential actin-binding proteins.35,37,38 These experiments led to the identification of a subset of heterogeneous nuclear ribonucleoproteins (hnRNPs) which is in complex with actin. Within these hnRNP proteins, specific interactions of actin with the C. tentans hrp65–2, homolog to the vertebrate transcriptional co-activators PSF-NonO (polypyrimidine-tract-binding-protein-associated splicing factor-non-Pou-domain octamer-binding protein/p54nrb), and with the mammalian hnRNP U/SAF-A (Scaffold Attachment Factor-A) were found to be required for transcription elongation in living cells.37,38 The actin-hrp65 and actin-hnRNP U interactions are highly conserved occurring through a novel, yet uncharacterized actin binding motif located in the C-termini. These actin-hnRNP interactions promote recruitment of histone acetyl transferases (HATs).29,39 In mammals, the actin-hnRNP U interaction facilitates recruitment of the HAT PCAF which leads to H3K9 acetylation along the gene. What places this mechanism in the context of transcription elongation is the fact that the actin-hnRNP U interaction does not seem to take place at gene promoter. It rather occurs immediately after promoter clearance when the heptapeptide repeats of the C-terminal domain (CTD) of the RNA polymerase II are hyperphosphorylated on Ser2 and Ser5 (Fig. 1).29 Therefore, it seems that the primary outcome of this actin-based mechanism is to provide an open chromatin configuration which allows passage of the elongating polymerase to scan the gene and elongate the nascent transcript (Fig. 2). We define this open chromatin configuration required for transcription elongation as permissive chromatin.


Co-transcriptional nuclear actin dynamics.

Percipalle P - Nucleus (2012)

Figure 1. The possible contribution of actin in RNA polymerase II transcription activation. Top panel, monomeric actin interacts with the PSF/NonO complex to recruit the positive elongation factor P-TEFb with the subunit cdk9. This in turn leads to Ser2 phosphorylation within the heptapeptide repeats of the RNA polymerase II CTD. This mechanism promotes RNA polymerase II CTD escape from pausing. Bottom panel, the CTD associated-actin interacts with hnRNP U and this mechanism commits the hyperphosphorylated RNA polymerase II to transcription elongation through recruitment of the HAT PCAF. RNAPII, RNA polymerase II; U, hnRNP U; T, ATP-actin; P-S2, phosphorylated Ser2; P-S5, phosphorylated Ser5.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3585027&req=5

Figure 1: Figure 1. The possible contribution of actin in RNA polymerase II transcription activation. Top panel, monomeric actin interacts with the PSF/NonO complex to recruit the positive elongation factor P-TEFb with the subunit cdk9. This in turn leads to Ser2 phosphorylation within the heptapeptide repeats of the RNA polymerase II CTD. This mechanism promotes RNA polymerase II CTD escape from pausing. Bottom panel, the CTD associated-actin interacts with hnRNP U and this mechanism commits the hyperphosphorylated RNA polymerase II to transcription elongation through recruitment of the HAT PCAF. RNAPII, RNA polymerase II; U, hnRNP U; T, ATP-actin; P-S2, phosphorylated Ser2; P-S5, phosphorylated Ser5.
Mentions: Several reports support a role for actin in commitment and maintenance of transcription elongation. The positive elongation factor P-TEFb, required by the RNA polymerase II for escape from pausing, is recruited via polymerase-associated actin, a mechanism that leads to hyperphosphorylation of the CTD and commitment to elongation (Fig. 1).36 To find out how actin actually functions in transcription elongation, nuclear RNP preparations from both C. tentans and mammalian cells were screened by DNase I affinity chromatography to pull-down actin and potential actin-binding proteins.35,37,38 These experiments led to the identification of a subset of heterogeneous nuclear ribonucleoproteins (hnRNPs) which is in complex with actin. Within these hnRNP proteins, specific interactions of actin with the C. tentans hrp65–2, homolog to the vertebrate transcriptional co-activators PSF-NonO (polypyrimidine-tract-binding-protein-associated splicing factor-non-Pou-domain octamer-binding protein/p54nrb), and with the mammalian hnRNP U/SAF-A (Scaffold Attachment Factor-A) were found to be required for transcription elongation in living cells.37,38 The actin-hrp65 and actin-hnRNP U interactions are highly conserved occurring through a novel, yet uncharacterized actin binding motif located in the C-termini. These actin-hnRNP interactions promote recruitment of histone acetyl transferases (HATs).29,39 In mammals, the actin-hnRNP U interaction facilitates recruitment of the HAT PCAF which leads to H3K9 acetylation along the gene. What places this mechanism in the context of transcription elongation is the fact that the actin-hnRNP U interaction does not seem to take place at gene promoter. It rather occurs immediately after promoter clearance when the heptapeptide repeats of the C-terminal domain (CTD) of the RNA polymerase II are hyperphosphorylated on Ser2 and Ser5 (Fig. 1).29 Therefore, it seems that the primary outcome of this actin-based mechanism is to provide an open chromatin configuration which allows passage of the elongating polymerase to scan the gene and elongate the nascent transcript (Fig. 2). We define this open chromatin configuration required for transcription elongation as permissive chromatin.

Bottom Line: This high degree of promiscuity in the spectrum of protein-to-protein interactions correlates well with the conformational plasticity of actin and the ability to undergo regulated changes in its polymerization states.Several of the factors involved in controlling head-to-tail actin polymerization have been shown to be in the nucleus where they seem to regulate gene activity.By focusing on the multiple tasks performed by actin and actin-binding proteins, possible models of how actin dynamics controls the different phases of the RNA polymerase II transcription cycle are being identified.

View Article: PubMed Central - PubMed

Affiliation: Department of Cell and Molecular Biology, Karolinska Institute, Stockholm, Sweden. piergiorgio.percipalle@ki.se

ABSTRACT
Actin is a key player for nuclear structure and function regulating both chromosome organization and gene activity. In the cell nucleus actin interacts with many different proteins. Among these proteins several studies have identified classical nuclear factors involved in chromatin structure and function, transcription and RNA processing as well as proteins that are normally involved in controlling the actin cytoskeleton. These discoveries have raised the possibility that nuclear actin performs its multi task activities through tight interactions with different sets of proteins. This high degree of promiscuity in the spectrum of protein-to-protein interactions correlates well with the conformational plasticity of actin and the ability to undergo regulated changes in its polymerization states. Several of the factors involved in controlling head-to-tail actin polymerization have been shown to be in the nucleus where they seem to regulate gene activity. By focusing on the multiple tasks performed by actin and actin-binding proteins, possible models of how actin dynamics controls the different phases of the RNA polymerase II transcription cycle are being identified.

Show MeSH