G-quadruplexes within prion mRNA: the missing link in prion disease?

Abstract:

:Cellular ribonucleic acid (RNA) plays a crucial role in the initial conversion of cellular prion protein PrP(C) to infectious PrP(Sc) or scrapie. The nature of this RNA remains elusive. Previously, RNA aptamers against PrP(C) have been isolated and found to form G-quadruplexes (G4s). PrP(C) binding to G4 RNAs destabilizes its structure and is thought to trigger its conversion to PrP(Sc). Here it is shown that PrP messenger RNA (mRNA) itself contains several G4 motifs, located in the octarepeat region. Investigation of the RNA structure in one of these repeats by circular dichroism, nuclear magnetic resonance and ultraviolet melting studies shows evidence of G4 formation. In vitro translation of full-length PrP mRNA, naturally harboring five consecutive G4 motifs, was specifically affected by G4-binding ligands, lending support to G4 formation in PrP mRNA. A possible role of PrP binding to its own mRNA and the role of anti-prion drugs, many of which are G4-binding ligands, in prion disease are discussed.

journal_name

Nucleic Acids Res

journal_title

Nucleic acids research

authors

Olsthoorn RC

doi

10.1093/nar/gku559

subject

Has Abstract

pub_date

2014-08-01 00:00:00

pages

9327-33

issue

14

eissn

0305-1048

issn

1362-4962

pii

gku559

journal_volume

42

pub_type

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