Published online 27 October 2005
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Alternative splicing and nonsense-mediated mRNA decay regulate mammalian ribosomal gene expression
Dipartimento di Biochimica e Biotecnologie Mediche, Università Federico II via Sergio Pansini 5, Napoli 80131, Italy
*To whom correspondence should be addressed. Tel: +39 081 7463065; Fax: +39 081 7463074; Email: pietropaolo{at}dbbm.unina.it
Received May 30, 2005. Revised September 29, 2005. Accepted September 29, 2005.
Messenger RNAs containing premature stop codons are generally targeted for degradation through nonsense-mediated mRNA decay (NMD). This mechanism degrades aberrant transcripts derived from mutant genes containing nonsense or frameshift mutations. Wild-type genes also give rise to transcripts targeted by NMD. For example, some wild-type genes give rise to alternatively spliced transcripts that are targeted for decay by NMD. In Caenorhabditis elegans, the ribosomal protein (rp) L12 gene generates a nonsense codon-bearing alternatively spliced transcript that is induced in an autoregulatory manner by the rpL12 protein. By pharmacologically blocking the NMD pathway, we identified alternatively spliced mRNA transcripts derived from the human rpL3 and rpL12 genes that are natural targets of NMD. The deduced protein sequence of these alternatively spliced transcripts suggests that they are unlikely to encode functional ribosomal proteins. Overexpression of rpL3 increased the level of the alternatively spliced rpL3 mRNA and decreased the normally expressed rpL3. This indicates that rpL3 regulates its own production by a negative feedback loop and suggests the possibility that NMD participates in this regulatory loop by degrading the non-functional alternatively spliced transcript.
Correspondence may also be addressed to Giulia Russo. Tel: +39 081 7463061; Fax: +39 081 7463074; Email: russog{at}dbbm.unina.it
The authors wish it to be known that, in their opinion, the first two authors should be regarded as joint First Authors
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