Nucleocytoplasmic traffic of CPEB1 and accumulation in Crm1 nucleolar bodies.

The translational regulator CPEB1 plays a major role in the control of maternal mRNA in oocytes, as well as of subsynaptic mRNAs in neurons. Although mainly cytoplasmic, we found that CPEB1 protein is continuously shuttling between nucleus and cytoplasm. Its export is controlled by two redundant NES motifs dependent on the nuclear export receptor Crm1. In the nucleus, CPEB1 accumulates in a few foci most often associated with nucleoli. These foci are different from previously identified nuclear bodies. They contain Crm1 and were called Crm1 nucleolar bodies (CNoBs). CNoBs depend on RNA polymerase I activity, indicating a role in ribosome biogenesis. However, although they form in the nucleolus, they never migrate to the nuclear envelope, precluding a role as a mediator for ribosome export. They could rather constitute a platform providing factors for ribosome assembly or export. The behavior of CPEB1 in CNoBs raises the possibility that it is involved in ribosome biogenesis.

[1]  C. Oubridge,et al.  Identification of molecular contacts between the U1 A small nuclear ribonucleoprotein and U1 RNA. , 1991, The EMBO journal.

[2]  Alain Bernheim,et al.  High frequency trans-splicing in a cell line producing spliced and polyadenylated RNA polymerase I transcripts from an rDNA-myc chimeric gene , 2005, Nucleic acids research.

[3]  T. Cooper,et al.  Disruption of splicing regulated by a CUG-binding protein in myotonic dystrophy. , 1998, Science.

[4]  M. Gorospe,et al.  Translational Repression by RNA-Binding Protein TIAR , 2006, Molecular and Cellular Biology.

[5]  C. Paul,et al.  PHAX and CRM1 are required sequentially to transport U3 snoRNA to nucleoli. , 2004, Molecular cell.

[6]  Geppino Falco,et al.  Identification and Functional Outcome of mRNAs Associated with RNA-Binding Protein TIA-1 , 2005, Molecular and Cellular Biology.

[7]  E. Nishida,et al.  Nuclear export of actin: a novel mechanism regulating the subcellular localization of a major cytoskeletal protein , 1998, The EMBO journal.

[8]  F. Kano,et al.  Dual localization of the RNA binding protein CUGBP-1 to stress granule and perinucleolar compartment. , 2008, Experimental cell research.

[9]  Søren Brunak,et al.  NESbase version 1.0: a database of nuclear export signals , 2003, Nucleic Acids Res..

[10]  J. Richter,et al.  CPEB: a life in translation. , 2007, Trends in biochemical sciences.

[11]  J. Stévenin,et al.  TIA-1 and TIAR Activate Splicing of Alternative Exons with Weak 5′ Splice Sites followed by a U-rich Stretch on Their Own Pre-mRNAs* , 2001, The Journal of Biological Chemistry.

[12]  E. Korb,et al.  CPEB1 regulates β‐catenin mRNA translation and cell migration in astrocytes , 2008, Glia.

[13]  D. A. Smillie,et al.  RNA helicase p54 (DDX6) is a shuttling protein involved in nuclear assembly of stored mRNP particles. , 2002, Journal of cell science.

[14]  N. Standart,et al.  A conserved role of a DEAD box helicase in mRNA masking. , 2001, RNA.

[15]  S. Warren,et al.  The fragile X mental retardation protein is a ribonucleoprotein containing both nuclear localization and nuclear export signals. , 1996, Human molecular genetics.

[16]  J. Bachellerie,et al.  Alterations of nucleolar ultrastructure and ribosome biogenesis by actinomycin D. Implications for U3 snRNP function. , 1992, European journal of cell biology.

[17]  Valérie Choesmel,et al.  Nuclear export and cytoplasmic processing of precursors to the 40S ribosomal subunits in mammalian cells , 2005, The EMBO journal.

[18]  Gary D. Smith,et al.  Identification and characterization of the gene encoding human cytoplasmic polyadenylation element binding protein. , 2001, Gene.

[19]  C. Gespach,et al.  Nuclear bodies and compartments: functional roles and cellular signalling in health and disease. , 2004, Cellular signalling.

[20]  D. Weil,et al.  The translational regulator CPEB1 provides a link between dcp1 bodies and stress granules , 2005, Journal of Cell Science.

[21]  D. Weil,et al.  Translationally repressed mRNA transiently cycles through stress granules during stress. , 2008, Molecular biology of the cell.

[22]  F. Tamanini,et al.  Different targets for the fragile X-related proteins revealed by their distinct nuclear localizations. , 1999, Human molecular genetics.

[23]  E. Rajpert-De Meyts,et al.  Nuclear transit of human zipcode-binding protein IMP1. , 2003, The Biochemical journal.

[24]  Véronique Kruys,et al.  Identification of the sequence determinants mediating the nucleo-cytoplasmic shuttling of TIAR and TIA-1 RNA-binding proteins , 2005 .

[25]  R. Singer,et al.  Real-Time Visualization of ZBP1 Association with β-Actin mRNA during Transcription and Localization , 2003, Current Biology.

[26]  R. Méndez,et al.  Maskin is a CPEB-associated factor that transiently interacts with elF-4E. , 1999, Molecular cell.

[27]  T. Deerinck,et al.  The Dynamic Organization of the Perinucleolar Compartment in the Cell Nucleus , 1997, The Journal of cell biology.

[28]  G. Humphrey,et al.  Association of polyoma T antigen and DNA with the nuclear matrix from lytically infected 3T6 cells , 1980, Cell.

[29]  D. Tollervey,et al.  Nuclear Export of 60S Ribosomal Subunits Depends on Xpo1p and Requires a Nuclear Export Sequence-Containing Factor, Nmd3p, That Associates with the Large Subunit Protein Rpl10p , 2001, Molecular and Cellular Biology.

[30]  D. Weil,et al.  CPEB Interacts with an Ovary-specific eIF4E and 4E-T in Early Xenopus Oocytes* , 2007, Journal of Biological Chemistry.

[31]  Arlen W. Johnson,et al.  Coordinated nuclear export of 60S ribosomal subunits and NMD3 in vertebrates , 2003, The EMBO journal.

[32]  Montserrat Soler-López,et al.  Architecture of CRM1/Exportin1 suggests how cooperativity is achieved during formation of a nuclear export complex. , 2004, Molecular cell.

[33]  U. Kutay,et al.  Biogenesis and nuclear export of ribosomal subunits in higher eukaryotes depend on the CRM1 export pathway , 2003, Journal of Cell Science.