Human GTPases associate with RNA polymerase II to mediate its nuclear import

Clément Carré, Ramin Shiekhattar

Research output: Contribution to journalArticle

29 Citations (Scopus)

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 of GPN1 or GPN3 using small interfering RNAs led to decreased RNAPII levels in the nucleus and an accumulation of this enzyme in the cytoplasm of human cells. Furthermore, isolation of a GPN1/GPN3/RNAPII complex from stable cell lines expressing a dominant negative GPN1 harboring mutations in the GTP-binding pocket demonstrated a role for these proteins in nuclear import of RNAPII. Thus, GPN1/GPN3 define a new family of small GTPases that are specialized for the transport of RNA polymerase II into the nucleus.

Original languageEnglish (US)
Pages (from-to)3953-3962
Number of pages10
JournalMolecular and Cellular Biology
Volume31
Issue number19
DOIs
StatePublished - Oct 2011
Externally publishedYes

Fingerprint

Cell Nucleus Active Transport
RNA Polymerase II
GTP Phosphohydrolases
Monomeric GTP-Binding Proteins
Nucleocytoplasmic Transport Proteins
Nuclear RNA
Guanosine Triphosphate
Small Interfering RNA
Cytoplasm
RNA
Cell Line
Mutation
Enzymes

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

Cite this

Human GTPases associate with RNA polymerase II to mediate its nuclear import. / Carré, Clément; Shiekhattar, Ramin.

In: Molecular and Cellular Biology, Vol. 31, No. 19, 10.2011, p. 3953-3962.

Research output: Contribution to journalArticle

@article{d4866057087244ab85a8ade1d6ee53e9,
title = "Human GTPases associate with RNA polymerase II to mediate its nuclear import",
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 of GPN1 or GPN3 using small interfering RNAs led to decreased RNAPII levels in the nucleus and an accumulation of this enzyme in the cytoplasm of human cells. Furthermore, isolation of a GPN1/GPN3/RNAPII complex from stable cell lines expressing a dominant negative GPN1 harboring mutations in the GTP-binding pocket demonstrated a role for these proteins in nuclear import of RNAPII. Thus, GPN1/GPN3 define a new family of small GTPases that are specialized for the transport of RNA polymerase II into the nucleus.",
author = "Cl{\'e}ment Carr{\'e} and Ramin Shiekhattar",
year = "2011",
month = "10",
doi = "10.1128/MCB.05442-11",
language = "English (US)",
volume = "31",
pages = "3953--3962",
journal = "Molecular and Cellular Biology",
issn = "0270-7306",
publisher = "American Society for Microbiology",
number = "19",

}

TY - JOUR

T1 - Human GTPases associate with RNA polymerase II to mediate its nuclear import

AU - Carré, Clément

AU - Shiekhattar, Ramin

PY - 2011/10

Y1 - 2011/10

N2 - 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 of GPN1 or GPN3 using small interfering RNAs led to decreased RNAPII levels in the nucleus and an accumulation of this enzyme in the cytoplasm of human cells. Furthermore, isolation of a GPN1/GPN3/RNAPII complex from stable cell lines expressing a dominant negative GPN1 harboring mutations in the GTP-binding pocket demonstrated a role for these proteins in nuclear import of RNAPII. Thus, GPN1/GPN3 define a new family of small GTPases that are specialized for the transport of RNA polymerase II into the nucleus.

AB - 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 of GPN1 or GPN3 using small interfering RNAs led to decreased RNAPII levels in the nucleus and an accumulation of this enzyme in the cytoplasm of human cells. Furthermore, isolation of a GPN1/GPN3/RNAPII complex from stable cell lines expressing a dominant negative GPN1 harboring mutations in the GTP-binding pocket demonstrated a role for these proteins in nuclear import of RNAPII. Thus, GPN1/GPN3 define a new family of small GTPases that are specialized for the transport of RNA polymerase II into the nucleus.

UR - http://www.scopus.com/inward/record.url?scp=80053614676&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=80053614676&partnerID=8YFLogxK

U2 - 10.1128/MCB.05442-11

DO - 10.1128/MCB.05442-11

M3 - Article

C2 - 21768307

AN - SCOPUS:80053614676

VL - 31

SP - 3953

EP - 3962

JO - Molecular and Cellular Biology

JF - Molecular and Cellular Biology

SN - 0270-7306

IS - 19

ER -