An antisense noncoding RNA enhances translation via localized structural rearrangements of its cognate mRNA

The Plant Cell, vol. 33, pp. 1381–1397

Abstract

A large portion of eukaryotic genes are associated with noncoding, natural antisense transcripts (NATs). Despite sharing extensive sequence complementarity with their sense mRNAs, mRNA-NAT pairs elusively often evade dsRNA-cleavage and siRNA-triggered silencing. More surprisingly, some NATs enhance translation of their sense mRNAs by yet unknown mechanism(s). Here, we show that translation enhancement of the rice (Oryza sativa) PHOSPHATE1.2 (PHO1.2) mRNA is enabled by specific structural rearrangements guided by its noncoding antisense RNA (cis-NATpho1.2). Their interaction in vitro revealed no evidence of widespread intermolecular dsRNA formation, but rather specific local changes in nucleotide base pairing, leading to higher flexibility of PHO1.2 mRNA at a key high guanine-cytosine�(GC) regulatory region inhibiting translation, ∼350-nt downstream of the start codon. Sense-antisense RNA interaction increased formation of the 80S complex in PHO1.2, possibly by inducing structural rearrangement within this inhibitory region, thus making this mRNA more accessible to 60S. This work presents a framework for nucleotide resolution studies of functional mRNA-antisense pairs.

Authors 5

1. Rodrigo Siqueira Reis corresponding

   University of Lausanne

   Affiliation as printed

   Department of Plant Molecular Biology, University of Lausanne, 1015 Lausanne, Switzerland

2. Jules Deforges

   University of Lausanne

   Affiliation as printed

   Department of Plant Molecular Biology, University of Lausanne, 1015 Lausanne, Switzerland

3. Romy Schmidt Aachen Institute of Biology I

   RWTH Aachen University

   Affiliation as printed

   Institute of Biology I, RWTH Aachen University, 52074 Aachen, Germany

4. Jos H. M. Schippers

   Leibniz-Institut für Pflanzengenetik und Kulturpflanzenforschung (IPK)

   Affiliation as printed

   Department of Molecular Genetics, Leibniz Institute of Plant Genetics and Crop Plant Research (IPK), 06466 Gatersleben, Germany

5. Yves Poirier corresponding

   University of Lausanne

   Affiliation as printed

   Department of Plant Molecular Biology, University of Lausanne, 1015 Lausanne, Switzerland