Proliferating cells express mRNAs with shortened 3' untranslated regions and fewer microRNA target sites.
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.
Sandberg
Rickard
R
Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
Neilson
Joel R
JR
Sarma
Arup
A
Sharp
Phillip A
PA
Burge
Christopher B
CB
D020413:3' Untranslated Regions; D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology / Q000378:metabolism*; D002460:Cell Line; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002478:Cells, Cultured; D005786:Gene Expression Regulation; D006801:Humans; D008213:Lymphocyte Activation; D051379:Mice; D008810:Mice, Inbred C57BL; D035683:MicroRNAs / Q000378:metabolism*; D020411:Oligonucleotide Array Sequence Analysis; D026723:Polyadenylation; D012326:RNA Splicing; D012333:RNA, Messenger / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*
D020413:3' Untranslated Regions; D035683:MicroRNAs; D012333:RNA, Messenger