Abstract

Many orthopoxvirus messenger RNAs have an unusual nontemplated poly(A) tract of 5 to 40 residues at the 5' end. The precise function of this feature is unknown. Here we show that 5' poly(A) tracts are able to repress RNA decay by inhibiting 3'-to-5' exonucleases as well as decapping of RNA substrates. UV cross-linking analysis demonstrated that the Lsm complex associates with the 5' poly(A) tract. Furthermore, recombinant Lsm1–7 complex specifically binds 5' poly(A) tracts 10 to 21 nucleotides in length, consistent with the length of 5' poly(A) required for stabilization. Knockdown of Lsm1 abrogates RNA stabilization by the 5' poly(A) tract. We propose that the Lsm complex simultaneously binds the 3' and 5' ends of these unusual messenger RNAs and thereby prevents 3'-to-5' decay. The implications of this phenomenon for cellular mRNA decay are discussed.

1. Department of Microbiology, Immunology & Pathology, Colorado State University, Fort Collins, Colorado 80525, USA.
2. Vinca Institute of Nuclear Sciences, Laboratory of Molecular Biology and Endocrinology, Mihaila Petrovica Alasa 12-14, Belgrade, Serbia, PO Box 522-090.
3. Paul Scherrer Institut, Biomolecular Research, CH5232 Villigen, Switzerland.
4. New York University School of Medicine, Department of Microbiology, New York, New York 10016, USA.
5. Present addresses: New York University School of Medicine, Department of Microbiology, New York, New York 10016, USA (N.B.) and Universidade do Vale do Paraíba, IP&D, Av. Shishima Hifumi, 2911, Urbanova, CEP 12244-000, São José dos Campos, SP, Brazil (K.C.M.M.).
6. These authors contributed equally to this work.

Correspondence to: Jeffrey Wilusz¹ e-mail: jeffrey.wilusz@colostate.edu

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