Neuron-specific ELAV/Hu proteins suppress HuR mRNA during neuronal differentiation by alternative polyadenylation.

Published

Journal Article

The ubiquitously expressed RNA-binding protein HuR increases the stability and translation of mRNAs encoding growth regulatory proteins that promote proliferation in a variety of cell types. However, the three neuron-specific ELAV/Hu proteins, HuB, HuC and HuD, while binding to the same types of mRNAs, are required instead for neuronal differentiation, and it becomes difficult to reconcile these contrary functions when all four Hu proteins are expressed in the same neuron. HuR mRNA exists as three alternatively polyadenylated variants, a 1.5-kb testes-specific mRNA isoform, a ubiquitous 2.4-kb isoform and a 6.0-kb isoform that we now show is induced during neuronal differentiation and appears to be neuron-specific. This 6.0-kb neuron-specific mRNA isoform is inherently less stable and produces less HuR protein than the ubiquitous 2.4-kb mRNA. Furthermore, we show that neuronal HuB, HuC and HuD, as well as HuR itself, can bind at the 2.4-kb mRNA polyadenylation site, and when overexpressed can affect alternative polyadenylation to generate an extended HuR 3'-UTR that is translationally suppressed. We propose that the regulation of HuR protein expression by alternative polyadenylation allows neurons to post-transcriptionally regulate mRNAs-encoding factors required for proliferation versus differentiation to facilitate neuronal differentiation.

Full Text

Duke Authors

Cited Authors

  • Mansfield, KD; Keene, JD

Published Date

  • March 2012

Published In

Volume / Issue

  • 40 / 6

Start / End Page

  • 2734 - 2746

PubMed ID

  • 22139917

Pubmed Central ID

  • 22139917

Electronic International Standard Serial Number (EISSN)

  • 1362-4962

Digital Object Identifier (DOI)

  • 10.1093/nar/gkr1114

Language

  • eng

Conference Location

  • England