Page 3 - 72_04

An. R. Acad. Nac. Farm., 2006, 72: 563-581

Revisiones

Aberrant mRNA Stability Regulation in Human
Diseases

Recibido el 30 de noviembre de 2006
ISABEL LÓPEZ DE SILANES * and MANEL ESTELLER *
Cancer Epigenetics Laboratory, Spanish National Cancer Center

(CNIO), 28029 Madrid, Spain

ABSTRACT

mRNA stability is emerging as a fundamental and effective cellular tool to
regulate gene expression at posttranscriptional levels. mRNA stability is controlled
via orchestrated interactions between mRNA structural components (cis-elements)
and specific trans-acting factors. The most widespread and efficient determinant of
RNA stability are the adenylate and uridylate-rich elements (ARE) that, through
binding of ARE-binding proteins (AUBPs), modulate the stability of transcripts
and/or their translation. Alterations in any of these components can lead to disease.
Here, we review the genetic alterations in 3’UTR regulatory sequences as well as
the aberrant levels, subcellular localization, and posttranslational modifications
of AUBPs that are linked to human diseases. A thorough understanding of these
alterations and their impact on mRNA stability regulation will uncover promising
new targets for therapeutic intervention.

Key words: Post-transcriptional gene regulation.—RNA-binding proteins.—AU-
rich elements (ARE).—ARE-binding proteins (AUBPs).—Cancer.—Inflammation.—
Thalassemia.—Alzheimer disease.

* Corresponding authors:
Isabel López de Silanes: ilsilanes@cnio.es
Manel Esteller: mesteller@cnio.es
Cancer Epigenetics Laboratory, Spanish National Cancer Center (CNIO).
Melchor Fernández Almagro, 3 - 28029 Madrid (Spain).
Telf.: +34 91 224 20 27. Fax: +34 91 224 69 23.

563