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HAX ‐1 is a nucleocytoplasmic shuttling protein with a possible role in m RNA processing
Author(s) -
Grzybowska Ewa A.,
Zayat Valery,
Konopiński Ryszard,
Trębińska Alicja,
Szwarc Maria,
Sarnowska Elżbieta,
Macech Ewelina,
Korczyński Jarosław,
Knapp Anna,
Siedlecki Janusz A.
Publication year - 2013
Publication title -
the febs journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.981
H-Index - 204
eISSN - 1742-4658
pISSN - 1742-464X
DOI - 10.1111/febs.12066
Subject(s) - nuclear export signal , microbiology and biotechnology , messenger rna , rna binding protein , biology , gene isoform , untranslated region , rna , nuclear localization sequence , cell nucleus , cytoplasm , gene , biochemistry
HAX‐1 is a multi‐functional protein that is involved in the regulation of apoptosis, cell motility and calcium homeostasis. It is also reported to bind RNA: it associates with structural motifs present in the 3′ untranslated regions of at least two transcripts, but the functional significance of this binding remains unknown. Although HAX‐1 has been detected in various cellular compartments, it is predominantly cytoplasmic. Our detailed localization studies of HAX‐1 isoforms revealed partial nuclear localization, the extent of which depends on the protein isoform. Further studies demonstrated that HAX‐1 is in fact a nucleocytoplasmic shuttling protein, dependent on the exportin 1 nuclear export receptor. Systematic mutagenesis allowed identification of the two nuclear export signals in the HAX‐1 sequence. HAX‐1 nuclear accumulation was observed after inhibition of nuclear export by leptomycin B, but also after specific cellular stress. The biological role of HAX‐1 nuclear localization and shuttling remains to be established, but the HAX‐1 transcript‐binding properties suggest that it may be connected to mRNA processing and surveillance. In this study, HAX‐1 status was shown to influence mRNA levels of DNA polymerase β, one of the HAX‐1 mRNA targets, although this effect becomes pronounced only after specific stress is applied. Moreover, HAX‐1 tethering to the reporter transcript caused a significant decrease in its expression. Additionally, the HAX‐1 co‐localization with P‐body markers, reported here, implies a role in mRNA processing. These results suggest that HAX‐1 may be involved in the regulation of expression of bound transcripts, possibly as part of the stress response. Structured digital abstractHAX1 and DCP1A , colocalize by fluorescence microscopy (View Interaction: 1 , 2 ) HAX1 physically interacts with XPO1 by anti tagcoimmunoprecipitation ( View interaction )