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Nature Structural & Molecular Biology 14, 824–831 (1 September 2007) | doi:10.1038/nsmb1287

Lsm proteins bind and stabilize RNAs containing 5|[prime]| poly(A) tracts

Naomi Bergman , Karen C M Moraes , John R Anderson , Bozidarka Zaric , Christian Kambach , Robert J Schneider , Carol J Wilusz & Jeffrey Wilusz

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