Identification and characterization of RED120: A conserved PWI domain protein with links to splicing and 3′-end formation

Fortes, Puri; Longman, Dasa; McCracken, Susan; Ip, Joanna Y.; Poot, Raymond; Mattaj, Iain W.; Cáceres, Javier F.; Blencowe, Benjamin J.

doi:10.1016/j.febslet.2007.05.066

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Volume 581, Issue 16 , Pages 3087-3097, 26 June 2007

Identification and characterization of RED120: A conserved PWI domain protein with links to splicing and 3′-end formation

Edited by Ulrike Kutay

Puri Fortes
- Division of Gene Therapy and Hepatology, CIMA, University of Navarra, Pamplona 31008, Spain
- Gene Expression Programme, European Molecular Biology Laboratory, Heidelberg D-69117, Germany
- Corresponding authors. Fax: +34 948 194717 (P. Fortes); +1 416 978 8287 (B.J. Blencowe).
Dasa Longman
- MRC Human Genetics Unit, Edinburgh EH4 2XU, Scotland, UK
Susan McCracken
- Banting and Best Department of Medical Research, Centre for Cellular and Biomolecular Research, University of Toronto, Toronto, Ontario, Canada M5S 3E1
Joanna Y. Ip
- Banting and Best Department of Medical Research, Centre for Cellular and Biomolecular Research, University of Toronto, Toronto, Ontario, Canada M5S 3E1
Raymond Poot
- Gene Expression Programme, European Molecular Biology Laboratory, Heidelberg D-69117, Germany
Iain W. Mattaj
- Gene Expression Programme, European Molecular Biology Laboratory, Heidelberg D-69117, Germany
Javier F. Cáceres
- MRC Human Genetics Unit, Edinburgh EH4 2XU, Scotland, UK
Benjamin J. Blencowe
- Banting and Best Department of Medical Research, Centre for Cellular and Biomolecular Research, University of Toronto, Toronto, Ontario, Canada M5S 3E1
- Corresponding authors. Fax: +34 948 194717 (P. Fortes); +1 416 978 8287 (B.J. Blencowe).

Received 12 March 2007; received in revised form 23 May 2007; accepted 25 May 2007. published online 04 June 2007.

Abstract

Precursor (pre)-mRNA splicing can impact the efficiency of coupled steps in gene expression. SRm160 (SR-related nuclear matrix protein of 160kDa), is a splicing coactivator that also functions as a 3′-end cleavage-stimulatory factor. Here, we have identified an evolutionary-conserved SRm160-interacting protein, referred to as hRED120 (for human Arg/Glu/Asp-rich protein of 120kDa). hRED120 contains a conventional RNA recognition motif and, like SRm160, a PWI nucleic acid binding domain, suggesting that it has the potential to bridge different RNP complexes. Also, similar to SRm160, hRED120 associates with snRNP components, and remains associated with mRNA after splicing. Simultaneous suppression in Caenorhabditis elegans of the ortholog of hRED120 with the orthologs of splicing and 3′-end processing factors results in aberrant growth or developmental defects. These results suggest that RED120 may function to couple splicing with mRNA 3′-end formation.