3UTR - Tissue-specific choice of 3

From 01-01-2009 to 31-12-2012

Description

Recent investigation in our laboratory on a large set of microarray experiments from a panel of 24 mouse tissues/organs indicated that at least 600 genes are differentially expressed by a tissue-specific choice of length of the 3’ untranslated region (3’UTR) of mRNA.Even for the most ubiquitously used genes such as those encoding ribosomal proteins and subunits of the mitochondrial respiratory chain, the Affymetrix 430 2.0 arrays, which are primarily directed against the 3’ end of transcripts, revealed considerable variation across different mouse tissues (Thorrez et al (2008) PloS ONE in press). This suggests that also form any other housekeeping genes transcript variants exist that can be identical for the protein coding information, but are different in 3’UTR length. It is now generally accepted that the3’UTR plays a role in post-transcriptional regulation of mRNA, influencing life-span, translation and transport of the transcript. The molecular mechanism of this regulation relies on bindingsites within the 3’UTR sequence for microRNAs and RNA-binding proteins. MicroRNAs are small (21-23 nt) non-protein coding RNAs that regulate mRNA stability and translation of target transcripts.

The human genome currently is known to harbor 541 miRNA genes (MirBase:http://microrna.sanger.ac.uk/) and some of these are expressed in a tissue-specific manner(Landgraf et al (2007) Cell 129: 1401-1414). Furthermore, there are dozens of known 3’UTRmRNAbinding proteins that affect mRNA life span, or regulate subcellular localization (e.g. inneurons) or protein translation (McKee et al (2007) Cell Res 17:581-90). One early discovered example of such regulation in pancreatic beta cells involves the pyrimidine tract binding proteinPTB1 that is important for glucose and incretin hormone-dependent post-transcriptional regulation of insulin-biosynthesis (Knoch et al (2004) Nat Cell Biol. 6:207-214; Knoch et al(2006) Cell Metab. 3:123-134).

Another example of an mRNA binding protein is pumilio-2which plays an important role in proliferation and self-renewal of stem cells (Crittenden SL et al(2002) Nature 417(6889):660-663; www.genecards.org) and brain function (Muraro et al (2008)J Neurosci 28:2099-2109). This protein regulates translation of its target that it recognizes via16 nt motif in the 3’UTR that is similar to Nanos Response Element (Moore et al (2003) PNAS100: 538-543).

Team

• Yves Moreau, Co-promoter
• Lieven Thorrez, Coordinator
• Frans Schuit, Promoter (External)
• Sonia Leach, Team member

Financing

Funding: FWO - Research Foundation - Flanders

Program/Grant Type: FWO Research Grant - FWO Research Grant