In a given living cell, mRNAs are synthesized by the RNA- polymerase II and destroyed by different ribonucleases. When these two events occur at a constantrate, they give rise to a steady-state mRNA population for each unique transcript.Although variations in mRNA transcription rates are recognized for their central importance in controlling gene expression, the regulatory role of changes in mRNA decay rates has been until recently left unexplored.

It is becoming clear that the half-life of a particular mRNA depends on sequences in the transcript itself, generally located in the 3’ untranslated region (3’UTR), and on RNA-binding proteins that bind to these sequences. The interplay between the 3’UTR sequence and different RNA-binding proteins (some promoting RNA decay and others increasing stability) determines the half-life of each specific transcript. The most studied 3’UTR motif involved in mRNA stability is the Adenylate/Uridylate-Rich Element (ARE). These AU-rich sequences have been shown to confer a very short half-life to mRNAs. Interestingly, when stabilizing RNA-binding proteins bind to these sequences, the half-life of the mRNA is dramatically increased. ARE are found mostly in oncogenes, immediate early genes, and cytokines, all genes with very rapid induction and repression. Moreover, it has also been hypothesized that all the mRNAs that are regulated by the same posttranscriptional mechanism comprise a post-transcriptional operon, a group of genes with similar regulation and functions.

We are studying how these post-transcriptional mechanisms operate in the

mammalian brain and how they are abnormal in pathological conditions.

Supported by:

Research Allocation Committee University of New Mexico (RAC)

The Childhood Brain Tumor Foundation