Sometimes Less Is More

Science Signaling  24 Jun 2008:
Vol. 1, Issue 25, pp. ec233
DOI: 10.1126/scisignal.125ec233

The 3′ untranslated regions (3′UTRs) of mRNAs contain sequences that influence the stability, subcellular localization, and translation of the mRNAs. Transcript isoforms that encode the same protein but differ in their 3′UTRs, therefore, often result in differences in protein production. Sandberg et al. examined the changes in expression of mRNA isoforms that accompany activation of T lymphocytes. Activation resulted in the increased abundance of isoforms with shorter 3′UTRs relative to those with longer 3′UTRs as measured 48 hours after activation. These shorter 3′UTRs lacked regulatory elements, such as microRNA (miRNA) target sites, through which translation is inhibited. Luciferase reporter assays confirmed that more protein is produced from constructs that contained shorter rather than longer 3′UTRs, presumably because the longer UTRs contained inhibitory regulatory elements. In the case of Hip2, deleting miRNA target sites from a long 3′UTR resulted in the production of protein that was similar in abundance to that produced from the short isoform 3′UTR transcripts. Thus, producing mRNAs with shorter 3′UTRs in response to activation may serve as a global cellular mechanism to increase protein abundance as the cells begin to proliferate. This phenomenon was observed in immune cell activation in both humans and mice and correlated with proliferation in many different cell types.

R. Sandberg, J. R. Neilson, A. Sarma, P. A. Sharp, C. B. Burge, Proliferating cells express mRNAs with shortened 3′ untranslated regions and fewer microRNA target sites. Science 320, 1643-1647 (2008). [Abstract] [Full Text]