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VOL. 72 (4), 563-581, 2006 ABERRANT MRNA STABILITY REGULATION IN HUMAN...

between the nucleus and the cytoplasm. Their cytoplasmic presence
appears to be intimately linked to their influence upon target mRNAs
and hence AUBPs localization has been the subject of gene
expression studies, specially in cancer. AUBS are also targeted for
posttranslational modifications, influencing AUBP ability to bind
to target mRNAs as well as their subcellular location. Increasing
evidence supports the notion that several RNA-binding proteins can
bind to a common ARE-containing target mRNA on both distict,
nonoverlapping sites, and on common sites in a competitive fashion.
It is becoming increasing apparent that the composition and fate
(stability, translation) of ribonucleoprotein complexes depend on
the target mRNA of interest, RNA-binding protein abundance, stress
conditions, and subcellular compartment. While AUBPs regulate
numerous posttranscriptional aspects of the mRNA (such as splicing,
mRNA localization, and mRNA storage), this review will focus on
the literature describing their influence on mRNA stability and
translation (8-10).

Given the aforementioned involvement of 3’UTR cis-elements and
trans-acting factors in dictating mRNA stability and translation,
it is easy to envision how alterations in any of these components
can have a major impact on mRNA half-life and/or translation.
In turn, defective mRNA turnover can cause abnormal stabilization
or decay of mRNAs, while disregulated translation can elevate or
lower translation rates. Together, these anomalous processes will
result in aberrant levels of expressed protein and hence metabolic
changes leading to disease. Defective mRNA half-life and translation
can arise from 1) Mutations in regulatory cis-elements (e.g., AREs)
such as single-point mutations, large deletions/insertions and
polymorphisms, and 2) alterations in trans-acting factors (e.g.,
AUBPs) such as defective expression and/or subcellular localization
of trans-acting factor, altered pattern of posttranslational
modifications, and aberrant competition among AUBPs which will
ultimately influence their net influence upon the fate of the mRNA
(stabilization, translation) (Fig. 1B). In human diseases, alterations
in both cis-elements and trans-acting factors have been described
(2-5). The purpose of this review is, therefore, to examine the altered
mRNA stability and/or translation regulation mediated, mainly, by
ARE determinants that can be found in human diseases. Identifying

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