PMID- 28592444
OWN - NLM
STAT- MEDLINE
DCOM- 20170913
LR  - 20191210
IS  - 1540-8140 (Electronic)
IS  - 0021-9525 (Print)
IS  - 0021-9525 (Linking)
VI  - 216
IP  - 7
DP  - 2017 Jul 3
TI  - Cellular differentiation state modulates the mRNA export activity of SR proteins.
PG  - 1993-2009
LID - 10.1083/jcb.201610051 [doi]
AB  - SR proteins function in nuclear pre-mRNA processing, mRNA export, and 
      translation. To investigate their cellular dynamics, we developed a quantitative 
      assay, which detects differences in nucleocytoplasmic shuttling among seven 
      canonical SR protein family members. As expected, SRSF2 and SRSF5 shuttle poorly 
      in HeLa cells but surprisingly display considerable shuttling in pluripotent 
      murine P19 cells. Combining individual-resolution cross-linking and 
      immunoprecipitation (iCLIP) and mass spectrometry, we show that elevated arginine 
      methylation of SRSF5 and lower phosphorylation levels of cobound SRSF2 enhance 
      shuttling of SRSF5 in P19 cells by modulating protein-protein and protein-RNA 
      interactions. Moreover, SRSF5 is bound to pluripotency-specific transcripts such 
      as Lin28a and Pou5f1/Oct4 in the cytoplasm. SRSF5 depletion reduces and 
      overexpression increases their cytoplasmic mRNA levels, suggesting that enhanced 
      mRNA export by SRSF5 is required for the expression of pluripotency factors. 
      Remarkably, neural differentiation of P19 cells leads to dramatically reduced 
      SRSF5 shuttling. Our findings indicate that posttranslational modification of SR 
      proteins underlies the regulation of their mRNA export activities and 
      distinguishes pluripotent from differentiated cells.
CI  - (c) 2017 Botti et al.
FAU - Botti, Valentina
AU  - Botti V
AUID- ORCID: 0000-0001-7407-8749
AD  - Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, 
      CT.
FAU - McNicoll, Francois
AU  - McNicoll F
AUID- ORCID: 0000-0001-5150-6245
AD  - Cluster of Excellence Macromolecular Complexes, Institute of Cell Biology and 
      Neuroscience, Goethe University Frankfurt, Frankfurt am Main, Germany.
FAU - Steiner, Michaela C
AU  - Steiner MC
AD  - Max Planck Institute of Molecular Cell Biology and Genetics, Dresden, Germany.
FAU - Richter, Florian M
AU  - Richter FM
AUID- ORCID: 0000-0002-9243-0272
AD  - Functional Proteomics Group, Institute for Biochemistry I, Goethe University 
      Frankfurt, Frankfurt am Main, Germany.
FAU - Solovyeva, Anfisa
AU  - Solovyeva A
AD  - Cluster of Excellence Macromolecular Complexes, Institute of Cell Biology and 
      Neuroscience, Goethe University Frankfurt, Frankfurt am Main, Germany.
FAU - Wegener, Marius
AU  - Wegener M
AD  - Cluster of Excellence Macromolecular Complexes, Institute of Cell Biology and 
      Neuroscience, Goethe University Frankfurt, Frankfurt am Main, Germany.
AD  - Buchmann Institute for Molecular Life Sciences, Frankfurt am Main, Germany.
FAU - Schwich, Oliver D
AU  - Schwich OD
AD  - Cluster of Excellence Macromolecular Complexes, Institute of Cell Biology and 
      Neuroscience, Goethe University Frankfurt, Frankfurt am Main, Germany.
AD  - Buchmann Institute for Molecular Life Sciences, Frankfurt am Main, Germany.
FAU - Poser, Ina
AU  - Poser I
AD  - Max Planck Institute of Molecular Cell Biology and Genetics, Dresden, Germany.
FAU - Zarnack, Kathi
AU  - Zarnack K
AD  - Buchmann Institute for Molecular Life Sciences, Frankfurt am Main, Germany.
FAU - Wittig, Ilka
AU  - Wittig I
AD  - Functional Proteomics Group, Institute for Biochemistry I, Goethe University 
      Frankfurt, Frankfurt am Main, Germany.
FAU - Neugebauer, Karla M
AU  - Neugebauer KM
AUID- ORCID: 0000-0002-3835-6761
AD  - Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, 
      CT karla.neugebauer@yale.edu.
FAU - Muller-McNicoll, Michaela
AU  - Muller-McNicoll M
AUID- ORCID: 0000-0002-7174-8310
AD  - Cluster of Excellence Macromolecular Complexes, Institute of Cell Biology and 
      Neuroscience, Goethe University Frankfurt, Frankfurt am Main, Germany 
      mueller-mcnicoll@bio.uni-frankfurt.de.
LA  - eng
PT  - Comparative Study
PT  - Journal Article
DEP - 20170607
PL  - United States
TA  - J Cell Biol
JT  - The Journal of cell biology
JID - 0375356
RN  - 0 (DNA-Binding Proteins)
RN  - 0 (NFX1 protein, human)
RN  - 0 (Nfx1 protein, mouse)
RN  - 0 (RNA, Messenger)
RN  - 0 (RNA-Binding Proteins)
RN  - 0 (Repressor Proteins)
RN  - 0 (SRSF2 protein, mouse)
RN  - 0 (SRSF5 protein, human)
RN  - 0 (SRSF5 protein, mouse)
RN  - 0 (Transcription Factors)
RN  - 147153-65-9 (SRSF2 protein, human)
RN  - 170974-22-8 (Serine-Arginine Splicing Factors)
RN  - 94ZLA3W45F (Arginine)
SB  - IM
MH  - Active Transport, Cell Nucleus
MH  - Animals
MH  - Arginine
MH  - *Cell Differentiation
MH  - Cell Nucleus/*metabolism
MH  - DNA-Binding Proteins/genetics/metabolism
MH  - HeLa Cells
MH  - Humans
MH  - Immunoprecipitation
MH  - Methylation
MH  - Mice
MH  - Neurogenesis
MH  - Phenotype
MH  - Phosphorylation
MH  - Pluripotent Stem Cells/*metabolism
MH  - Protein Binding
MH  - Protein Processing, Post-Translational
MH  - RNA Interference
MH  - RNA, Messenger/genetics/*metabolism
MH  - RNA-Binding Proteins/genetics/metabolism
MH  - Repressor Proteins/genetics/metabolism
MH  - Serine-Arginine Splicing Factors/genetics/*metabolism
MH  - Tandem Mass Spectrometry
MH  - Transcription Factors/genetics/metabolism
MH  - Transfection
PMC - PMC5496613
EDAT- 2017/06/09 06:00
MHDA- 2017/09/14 06:00
PMCR- 2018/01/03
CRDT- 2017/06/09 06:00
PHST- 2016/10/15 00:00 [received]
PHST- 2017/03/22 00:00 [revised]
PHST- 2017/04/24 00:00 [accepted]
PHST- 2017/06/09 06:00 [pubmed]
PHST- 2017/09/14 06:00 [medline]
PHST- 2017/06/09 06:00 [entrez]
PHST- 2018/01/03 00:00 [pmc-release]
AID - jcb.201610051 [pii]
AID - 201610051 [pii]
AID - 10.1083/jcb.201610051 [doi]
PST - ppublish
SO  - J Cell Biol. 2017 Jul 3;216(7):1993-2009. doi: 10.1083/jcb.201610051. Epub 2017 
      Jun 7.