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Published on: July 7, 2010
The RGG domain in hnRNP A2 affects subcellular localization
R C Nichols1, X W Wang, J Tang
1Section of Connective Tissue Diseases, Dartmouth Medical School, Lebanon, New Hampshire 03756, USA. ralph.c.nichols@dartmouth.edu
Experimental Cell Research
|April 25, 2000
Summary
Arginine methylation regulates the nuclear export of hnRNP A2, a lung cancer biomarker. Deleting the RGG domain causes cytoplasmic localization, suggesting a novel methylation-regulated nuclear localization sequence.
Area of Science:
- Molecular Biology
- Cell Biology
- Biochemistry
Background:
- Heterogeneous nuclear ribonucleoproteins (hnRNPs) are crucial for RNA processing and transport.
- hnRNP A2 overexpression is an early lung cancer biomarker and is implicated in brain tumors.
- The nucleocytoplasmic localization of hnRNP A2 is not well understood.
Purpose of the Study:
- To investigate the role of arginine methylation in the nucleocytoplasmic localization of hnRNP A2.
- To identify the specific domain of hnRNP A2 involved in its localization.
- To explore potential novel localization signals regulated by methylation.
Main Methods:
- HEK-293 and NIH-3T3 cells were treated with a methyltransferase inhibitor (adenosine dialdehyde).
- hnRNP A2 localization was assessed using immunoblotting and immunocytochemistry.
- In vitro methylation assays with PRMT1 and analysis of hnRNP A2 RGG mutants were performed.
Main Results:
- Inhibition of methylation caused a dramatic shift of hnRNP A2 from the nucleus to the cytoplasm.
- hnRNP A2 was identified as a substrate for PRMT1, with methylation occurring in the RGG domain.
- Deletion of the RGG domain (residues 191-253) resulted in a cytoplasmic localization phenotype.
Conclusions:
- Arginine methylation of the RGG domain is critical for the nuclear localization of hnRNP A2.
- The RGG domain contains sequences essential for hnRNP A2 cellular localization.
- A novel, methylation-regulated nuclear localization sequence may exist within the RGG domain of hnRNP A2.
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