JCB logo
HYBRIGENICS
  Home | Help | Feedback | Subscriptions | Archive | Search | Table of Contents
This Article
Right arrow Full Text
Right arrow PDF (Full Text)
Right arrow Alert me when this article is cited
Right arrow Citation Map
Services
Right arrow Email this article
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new content in the JCB
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via CrossRef
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Kedersha, N. L.
Right arrow Articles by Anderson, P.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Kedersha, N. L.
Right arrow Articles by Anderson, P.
Social Bookmarking
Add to CiteULike   Add to Complore   Add to Connotea   Add to Del.icio.us   Add to Digg   Add to Reddit   Add to Technorati  
What's this?
© The Rockefeller University Press, 0021-9525/1999/12/1431/ $5.00
The Journal of Cell Biology, Volume 147, Number 7, December 27, 1999 1431-1442

Original Article

RNA-binding Proteins TIA-1 and TIAR Link the Phosphorylation of eIF-2{alpha} to the Assembly of Mammalian Stress Granules

Nancy L. Kedershaa, Mita Guptaa, Wei Lia, Ira Millera, and Paul Andersona
a Division of Rheumatology and Immunology, Brigham and Women's Hospital, Smith Building, Boston, Massachusetts 02115

Correspondence to: Paul Anderson, Division of Rheumatology and Immunology, Brigham and Women's Hospital, Smith 652, 75 Francis Street, Boston, MA 02115. Tel:(617) 525-1202 Fax:(617) 525-1310 E-mail:panderson{at}rics.bwh.harvard.edu.

In response to environmental stress, the related RNA-binding proteins TIA-1 and TIAR colocalize with poly(A)+ RNA at cytoplasmic foci that resemble the stress granules (SGs) that harbor untranslated mRNAs in heat shocked plant cells (Nover et al. 1989 Down; Nover et al. 1983 Down; Scharf et al. 1998 Down). The accumulation of untranslated mRNA at SGs is reversible in cells that recover from a sublethal stress, but irreversible in cells subjected to a lethal stress. We have found that the assembly of TIA-1/R+ SGs is initiated by the phosphorylation of eIF-2{alpha}. A phosphomimetic eIF-2{alpha} mutant (S51D) induces the assembly of SGs, whereas a nonphosphorylatable eIF-2{alpha} mutant (S51A) prevents the assembly of SGs. The ability of a TIA-1 mutant lacking its RNA-binding domains to function as a transdominant inhibitor of SG formation suggests that this RNA-binding protein acts downstream of the phosphorylation of eIF-2{alpha} to promote the sequestration of untranslated mRNAs at SGs. The assembly and disassembly of SGs could regulate the duration of stress- induced translational arrest in cells recovering from environmental stress.

Key Words: RNA-binding proteins, stress, translational control, eIF-2{alpha}


Add to CiteULike CiteULike   Add to Complore Complore   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us   Add to Digg Digg   Add to Reddit Reddit   Add to Technorati Technorati    What's this?


This article has been cited by other articles:



  Home | Help | Feedback | Subscriptions | Archive | Search | Table of Contents