Human GTPases Associate with RNA Polymerase II To Mediate Its Nuclear Import

@article{Carr2011HumanGA,
  title={Human GTPases Associate with RNA Polymerase II To Mediate Its Nuclear Import},
  author={Cl{\'e}ment Carr{\'e} and Ramin Shiekhattar},
  journal={Molecular and Cellular Biology},
  year={2011},
  volume={31},
  pages={3953 - 3962}
}
ABSTRACT Small GTPases share a biochemical mechanism and act as binary molecular switches. One important function of small GTPases in the cell is nucleocytoplasmic transport of both proteins and RNA. Here, we show the stable association of human GPN1 and GPN3, small GTPases related to Ran, with RNA polymerase II (RNAPII) isolated from either the cytoplasmic or nuclear fraction. GPN1 and GPN3 directly interact with RNAPII subunit 7 (RPB7)/RPB4 and the C-terminal domain (CTD) of RNAPII. Depletion… 
Biogenesis of RNA Polymerases II and III Requires the Conserved GPN Small GTPases in Saccharomyces cerevisiae
TLDR
This study shows that the nuclear import defect of iwr1Δ, but not the GPN2 or GPN3 mutant defects, is partially suppressed by fusion of a nuclear localization signal to the RNA polymerase II subunit Rpb3, and suggests that theGPN proteins function upstream of Iwr1 in RNA polymerases II and III biogenesis.
Npa3 interacts with Gpn3 and assembly factor Rba50 for RNA polymerase II biogenesis
TLDR
It is shown here that rapid degradation of each GPN protein in yeast leads to cytoplasmic accumulation of Rpb1 and defects in the assembly of RNA polymerase II, suggesting conserved functions of GPN paralogs for RNA polymerases II biogenesis as in humans.
Nuclear import of RNA polymerase II is coupled with nucleocytoplasmic shuttling of the RNA polymerase II-associated protein 2
TLDR
The results have important implications, as they indicate that RPAP2 controls gene expression by two distinct mechanisms, one that targetsRNAP II activity during transcription and the other that controls availability of RNAP II in the nucleus.
Proteomic Analysis Reveals a Role for the GTPase RPAP4/GPN1 and the Cochaperone RPAP3 in Biogenesis of All Three Nuclear RNA Polymerases
TLDR
A model in which biogenesis of RNAP I, II and III is integrated through the action of assembly and nuclear import factors is presented, suggesting that all three nuclear RNAPs may be coupled.
Rtp1p Is a Karyopherin-Like Protein Required for RNA Polymerase II Biogenesis
TLDR
Rtp1p is defined as a new component of the RNA pol II biogenesis machinery that plays roles in subunit assembly and likely in transport through the nuclear pore complex.
Structure of GPN-Loop GTPase Npa3 and Implications for RNA Polymerase II Assembly
TLDR
It is shown that Npa3 has chaperone activity and interacts with hydrophobic peptide regions of Pol II subunits that form interfaces in the assembled Pol II complex, suggesting that GPN-loop GTPases are assembly chaperones for Pol II and other protein complexes.
Human RNA polymerase II-associated protein 2 (RPAP2) interacts directly with the RNA polymerase II subunit Rpb6 and participates in pre-mRNA 3'-end formation.
TLDR
It is demonstrated that the C-terminal region of RPAP2 interacts directly with the Pol II subunit Rpb6 and participates in pre-mRNA 3'-end formation.
...
...

References

SHOWING 1-10 OF 27 REFERENCES
The Protein Interaction Network of the Human Transcription Machinery Reveals a Role for the Conserved GTPase RPAP4/GPN1 and Microtubule Assembly in Nuclear Import and Biogenesis of RNA Polymerase II*
TLDR
RPAP4/GPN1 is a member of a newly discovered GTPase family that contains a unique and highly conserved GPN loop motif that is essential, in conjunction with its GTP-binding motifs, for nuclear localization of POLR2A/RPB1 in a process that also requires microtubule assembly.
Rpb7 subunit of RNA polymerase II interacts with an RNA-binding protein involved in processing of transcripts.
TLDR
The results suggest that Rpb7 may function to anchor a processing factor to the pol II apparatus, thereby coupling RNA processing to transcription, consistent with its location in thePol II complex determined by recent structural studies.
RPAP1, a Novel Human RNA Polymerase II-Associated Protein Affinity Purified with Recombinant Wild-Type and Mutated Polymerase Subunits
TLDR
A role forRPAP1 in RNAPII transcription was established by shutting off the synthesis of Ydr527wp, a Saccharomyces cerevisiae protein homologous to RPAP1, and demonstrating that changes in global gene expression were similar to those caused by the loss of the yeastRNAPII subunit Rpb11.
Unstructured N Terminus of the RNA Polymerase II Subunit Rpb4 Contributes to the Interaction of Rpb4·Rpb7 Subcomplex with the Core RNA Polymerase II of Saccharomyces cerevisiae*
TLDR
It is shown that the weak interaction predicted for the N-terminal region of Rpb4 with Rpb2 in the crystal structure actually plays a significant role in interaction of the subcomplex with the core in vivo.
RPB7, one of two dissociable subunits of yeast RNA polymerase II, is essential for cell viability
TLDR
The results suggest that RPB7 contributes to the function of RNA polymerase II in the absence of RPB4 either in a manner independent of its association with the enzyme or by directly binding to the enzyme in a way independent ofIts association with RPB 4.
The Rpb4 Subunit of RNA Polymerase II Contributes to Cotranscriptional Recruitment of 3′ Processing Factors
TLDR
Results indicate that Rpb4 contributes to proper cotranscriptional 3′-end processing in vivo, as well as recruitment of other protein factors involved in transcription.
A T42A Ran mutation: differential interactions with effectors and regulators, and defect in nuclear protein import.
TLDR
The properties of T42A-Ran are consistent with its classification as an effector mutant and define the exposed region of Ran containing the mutation as a probable effector loop.
Inhibition of nuclear protein import by nonhydrolyzable analogues of GTP and identification of the small GTPase Ran/TC4 as an essential transport factor [published erratum appears in J Cell Biol 1994 Jan;124(1-2):217]
TLDR
The results suggest that Ran/TC4 serves to integrate nuclear protein import with these other nuclear activities, and may be implicated in DNA replication, cell cycle checkpoint control, and RNA synthesis, processing and export.
Analysis of the Interaction of the Novel RNA Polymerase II (pol II) Subunit hsRPB4 with Its Partner hsRPB7 and with pol II
TLDR
hsRPB4 expression in humans parallels that of hsRPB7, supporting the idea that the two proteins may possess associated functions, and should provide the basis for subsequent structural and functional characterization of the pol II holoenzyme.
...
...