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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 5. Speculative model on the dynamic actin polymerization during transcription. In the initial phases of transcription actin is in a monomeric form. This actin fraction contributes to PIC assembly and to facilitate transcription initiation. Upon commitment of the polymerase enzyme to elongation, actin polymerization accompanies the elongation process in a treadmilling regime which is controlled by cofilin and profilin. This mechanism is reiterated throughout the entire length of the transcribed gene. For termination we speculate that a yet unidentified mechanism at the anchorage point of polymeric actin leads to disassembly of actin polymers and contributes to transcription termination. D, ADP-actin; T, ATP-actin; C, cofilin; P, profilin.
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Figure 5: Figure 5. Speculative model on the dynamic actin polymerization during transcription. In the initial phases of transcription actin is in a monomeric form. This actin fraction contributes to PIC assembly and to facilitate transcription initiation. Upon commitment of the polymerase enzyme to elongation, actin polymerization accompanies the elongation process in a treadmilling regime which is controlled by cofilin and profilin. This mechanism is reiterated throughout the entire length of the transcribed gene. For termination we speculate that a yet unidentified mechanism at the anchorage point of polymeric actin leads to disassembly of actin polymers and contributes to transcription termination. D, ADP-actin; T, ATP-actin; C, cofilin; P, profilin.

Mentions: In summary during the RNA polymerase II transcription cycle, a key role for actin has been demonstrated for PIC formation and in the post-initiation phases to facilitate escape from pausing and elongation (Fig. 3). However, we would like to propose that regulated actin polymerization is not a requirement for transcription initiation but it affects the later phases of gene transcription. We hypothesize that regulated actin polymerization is needed for the transition from initiation to elongation and to maintain productive transcription elongation (see Figure 5). These mechanisms appear to be isoform-specific for β-actin as the other non-muscle form, γ-actin, has not been implicated in gene expression regulation in vivo.32 Whether these mechanisms support only gene activation and not gene repression is a fascinating question for future work. As mentioned earlier a recent β-actin knockout mouse model demonstrated that in vivo, the primary task of β-actin is not to promote cell motility but it is required for gene activity.32 Remarkably, in this study the authors found that the lack of β-actin leads to both activation and repression of different sets of genes. This finding is compatible with a dual role for β-actin as activator and repressor of gene transcription. How this dual function is exerted in the same nuclear context is a matter of speculation. An attractive possibility is that it is precisely the control of head-to-tail actin polymerization along a gene that contributes to set the rules as to whether the gene is activated or repressed via an actin-based mechanism. Changes in the rate of actin depolymerization from the pointed ends may ultimately affect the spatial distribution of the polymerase machinery and lead either to a stall or to higher polymerase processivity. In this scenario, cofilin becomes a central player in the regulation of gene activity.


Co-transcriptional nuclear actin dynamics.

Percipalle P - Nucleus (2012)

Figure 5. Speculative model on the dynamic actin polymerization during transcription. In the initial phases of transcription actin is in a monomeric form. This actin fraction contributes to PIC assembly and to facilitate transcription initiation. Upon commitment of the polymerase enzyme to elongation, actin polymerization accompanies the elongation process in a treadmilling regime which is controlled by cofilin and profilin. This mechanism is reiterated throughout the entire length of the transcribed gene. For termination we speculate that a yet unidentified mechanism at the anchorage point of polymeric actin leads to disassembly of actin polymers and contributes to transcription termination. D, ADP-actin; T, ATP-actin; C, cofilin; P, profilin.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 5: Figure 5. Speculative model on the dynamic actin polymerization during transcription. In the initial phases of transcription actin is in a monomeric form. This actin fraction contributes to PIC assembly and to facilitate transcription initiation. Upon commitment of the polymerase enzyme to elongation, actin polymerization accompanies the elongation process in a treadmilling regime which is controlled by cofilin and profilin. This mechanism is reiterated throughout the entire length of the transcribed gene. For termination we speculate that a yet unidentified mechanism at the anchorage point of polymeric actin leads to disassembly of actin polymers and contributes to transcription termination. D, ADP-actin; T, ATP-actin; C, cofilin; P, profilin.
Mentions: In summary during the RNA polymerase II transcription cycle, a key role for actin has been demonstrated for PIC formation and in the post-initiation phases to facilitate escape from pausing and elongation (Fig. 3). However, we would like to propose that regulated actin polymerization is not a requirement for transcription initiation but it affects the later phases of gene transcription. We hypothesize that regulated actin polymerization is needed for the transition from initiation to elongation and to maintain productive transcription elongation (see Figure 5). These mechanisms appear to be isoform-specific for β-actin as the other non-muscle form, γ-actin, has not been implicated in gene expression regulation in vivo.32 Whether these mechanisms support only gene activation and not gene repression is a fascinating question for future work. As mentioned earlier a recent β-actin knockout mouse model demonstrated that in vivo, the primary task of β-actin is not to promote cell motility but it is required for gene activity.32 Remarkably, in this study the authors found that the lack of β-actin leads to both activation and repression of different sets of genes. This finding is compatible with a dual role for β-actin as activator and repressor of gene transcription. How this dual function is exerted in the same nuclear context is a matter of speculation. An attractive possibility is that it is precisely the control of head-to-tail actin polymerization along a gene that contributes to set the rules as to whether the gene is activated or repressed via an actin-based mechanism. Changes in the rate of actin depolymerization from the pointed ends may ultimately affect the spatial distribution of the polymerase machinery and lead either to a stall or to higher polymerase processivity. In this scenario, cofilin becomes a central player in the regulation of gene activity.

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