[N1] The research was funded by the Knut och Alice Wallenbergs Stiftelse (Knut and Alice Wallenberg Foundation), the Cancer Research Institute, the Gina De Felice and Robert M. Lefkowitz Fund, the US Public Health Service (PHS), the US National Cancer Institute and the National Human Genome Research Institute (NHGRI).

[N2] Lead authors of the paper are Rickard Sandberg, a postdoctoral fellow in the Department of Biology, now at the Karolinska Institute in Sweden, and Joel Neilson, research scientist at MIT's David H. Koch Institute for Integrative Cancer Research. Other authors of the paper are MIT undergraduate Arup Sarma and Professor Sharp, Nobel laureate.

Proliferating cells express mRNAs with shortened 3' untranslated regions and fewer microRNA target sites. Rickard Sandberg, Joel R. Neilson, Arup Sarma, Phillip A. Sharp, Christopher B. Burge. Science 320, 1643-7.

Abstract

Messenger RNA (mRNA) stability, localization, and translation are largely determined by sequences in the 3' untranslated region (3'UTR). We found a conserved increase in expression of mRNAs terminating at upstream polyadenylation sites after activation of primary murine CD4+ T lymphocytes. This program, resulting in shorter 3'UTRs, is a characteristic of gene expression during immune cell activation and correlates with proliferation across diverse cell types and tissues. Forced expression of full-length 3'UTRs conferred reduced protein expression. In some cases the reduction in protein expression could be reversed by deletion of predicted microRNA target sites in the variably included region. Our data indicate that gene expression is coordinately regulated, such that states of increased proliferation are associated with widespread reductions in the 3'UTR-based regulatory capacity of mRNAs.