Poly(A)-binding protein modulates mRNA susceptibility to cap-dependent miRNA-mediated repression

Robert W. Walters, Shelton Bradrick, Matthias Gromeier

Research output: Contribution to journalArticle

48 Citations (Scopus)

Abstract

MicroRNAs (miRNAs) regulate gene expression post-transcriptionally through binding specific sites within the 3′ untranslated regions (UTRs) of their target mRNAs. Numerous investigations have documented repressive effects of miRNAs and identified factors required for their activity. However, the precise mechanisms by which miRNAs modulate gene expression are still obscure. Here, we have examined the effects of multiple miRNAs on diverse target transcripts containing artificial or naturally occurring 3′ UTRs in human cell culture. In agreement with previous studies, we report that both the 5′ m7G cap and 3′ poly(A) tail are essential for maximum miRNA repression. These cis-acting elements also conferred miRNA susceptibility to target mRNAs translating under the control of viral- and eukaryotic mRNA-derived 5′ UTR structures that enable cap-independent translation. Additionally, we evaluated a role for the poly(A)-binding protein (PABP) in miRNA function utilizing multiple approaches to modulate levels of active PABP in cells. PABP expression and activity inversely correlated with the strength of miRNA silencing, in part due to antagonism of target mRNA deadenylation. Together, these findings further define the cis- and trans-acting factors that modulate miRNA efficacy.

Original languageEnglish (US)
Pages (from-to)239-250
Number of pages12
JournalRNA
Volume16
Issue number1
DOIs
StatePublished - Jan 2010
Externally publishedYes

Fingerprint

Poly(A)-Binding Proteins
MicroRNAs
Messenger RNA
3' Untranslated Regions
Gene Expression
Trans-Activators
5' Untranslated Regions
Cell Culture Techniques
Binding Sites

Keywords

  • IRES
  • miRNA
  • PABP
  • Paip2
  • Poly(A)

ASJC Scopus subject areas

  • Molecular Biology
  • Medicine(all)

Cite this

Poly(A)-binding protein modulates mRNA susceptibility to cap-dependent miRNA-mediated repression. / Walters, Robert W.; Bradrick, Shelton; Gromeier, Matthias.

In: RNA, Vol. 16, No. 1, 01.2010, p. 239-250.

Research output: Contribution to journalArticle

Walters, Robert W. ; Bradrick, Shelton ; Gromeier, Matthias. / Poly(A)-binding protein modulates mRNA susceptibility to cap-dependent miRNA-mediated repression. In: RNA. 2010 ; Vol. 16, No. 1. pp. 239-250.
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