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Science 20 June 2008:
Vol. 320. no. 5883, pp. 1643 - 1647
DOI: 10.1126/science.1155390
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Reports

Proliferating Cells Express mRNAs with Shortened 3' Untranslated Regions and Fewer MicroRNA Target Sites

Rickard Sandberg,1*{dagger} Joel R. Neilson,2* Arup Sarma,3 Phillip A. Sharp,1,2{ddagger} Christopher B. Burge1{ddagger}

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.

1 Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
2 Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
3 Department of Electrical Engineering and Computer Science, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.

* These authors contributed equally to this work.

{dagger} Present address: Department of Cell and Molecular Biology, Karolinska Institutet, 171 77 Stockholm, Sweden.

{ddagger} To whom correspondence should be addressed. E-mail: sharppa{at}mit.edu (P.A.S.); cburge{at}mit.edu (C.B.B.)

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