CBB Seminar,  11:00 am, Tuesday  March 18th, B2 Library

Alissa M. Resch

Structural features in alternatively spliced and constitutive regions of mammalian 5’UTRs

 

Structural features located within the 5’UTR leader sequences of eukaryotic mRNAs have been shown to control translation of mRNA into protein. 
 Previous studies have shown that the occurrence of initiation codons (uAUGs) and open reading frames (uORFs) upstream of the authentic start
 codon may have an effect on the efficiency of translation.  In general, the presence of uAUGs and uORFs is associated with translational repression,
 however, cases of increased translational efficiency have also been identified.  

The abundance of uAUGs and uORFs in mammalian 5’UTRs, coupled with the observation that the majority of alternative splicing events in human 
occur in the 5’UTR, prompted us to investigate the organization of structural features within alternatively spliced and constitutive regions
 of mammalian 5’UTR sequences.  

We analyzed the 5’UTR leader sequences of a set of human and mouse genes known to possess alternatively spliced 5’UTRs.  Our data indicate
 that uAUGs and uORFs are present in roughly 50% of the genes included in our analysis, which is roughly consistent with estimates that 44%
 of human mRNAs contain uAUGs and uORFs.  We found that the ratio of alternative to constitutive nucleotides is much higher within the 5’UTR 
than for the corresponding coding regions of the genes included in our analysis.  Our data also show that alternatively spliced regions of 
the 5’UTR contain nearly twice as many uAUGs and uORFs than constitutive regions.  Additionally, we found that a substantial fraction of uAUGS 
and uORFs are conserved in both the alternatively spliced and constitutive regions of 5’UTR in both human-macaca and mouse-rat orthologs.  
Our evolutionary analysis of 5’UTRs indicates that alternatively spliced regions of the 5’UTR are evolving more rapidly than constitutive
 regions, consistent with the notion that alternative splicing is associated with increased evolutionary change.

Joint work with Svetlana Shabalina, Igor Rogozin, Alex Ogurtsov and Eugene Koonin.