mRNA surveillance of expressed pseudogenes in C-elegans

Messenger RNAs (mRNAs) that contain premature translation termination codons (PTCs) are targeted for rapid degradation in all eukaryotes tested. The mechanisms of nonsense-mediated mRNA decay (NMD) have been described in considerable detail [1, 2], but the biological roles of NMD in wild-type organisms are poorly understood. mRNAs of wild-type organisms known to be degraded by NMD (natural targets of NMD) include by-products of regulated alternative splicing [3-6], out-of-frame mRNAs derived from unproductive gene rearrangements [7, 8], cytoplasmic pre-mRNAs [9, 10], endogenous retroviral and transposon RNAs [11], and mRNAs having upstream open reading frames or other unusual sequence features [11-14]. NMD may function to eliminate aberrant PTC-containing mRNAs in order to protect cells from expression of potentially deleterious truncated proteins [15, 16]. Pseudogenes are nonfunctional genes or gene fragments that accumulate mutations through genetic drift [17]. Such mutations will often introduce shifts of reading frame and/ or PTCs, and mRNAs of expressed pseudogenes may thus be substrates of NIVID [18]. We demonstrate that mRNAs expressed from C. elegans pseudogenes are degraded by NIVID and discuss possible implications for both mRNA surveillance and protein evolution. We describe an expressed pseudogene that encodes a small nucleolar RNA (snoRNA) within an intron and suggest this represents an evolutionary intermediate between snoRNA-encoding host genes that do or do not encode proteins.