RNA splicing promotes translation and RNA surveillance.
Aberrant mRNAs harboring premature termination codons (PTCs or nonsense codons) are degraded by the nonsense-mediated mRNA decay (NMD) pathway. mRNAs transcribed from genes that naturally acquire PTCs during lymphocyte development are strongly downregulated by PTCs. Here we show that a signal essential for this robust mRNA downregulatory response is efficient RNA splicing. Strong mRNA downregulation can be conferred on a poor NMD substrate by either strengthening its splicing signals or removing its weak introns. Efficient splicing also strongly promotes translation, providing a molecular explanation for enhanced NMD and suggesting that efficient splicing may have evolved to enhance both protein production and RNA surveillance. Our results suggest simple approaches for increasing protein expression from expression vectors and treating human genetic diseases caused by nonsense and frameshift mutations.
Gudikote
Jayanthi P
JP
Department of Immunology, University of Texas M.D. Anderson Cancer Center, Houston, Texas 77030, USA.
Imam
J Saadi
JS
Garcia
Ramon F
RF
Wilkinson
Miles F
MF
D001483:Base Sequence; D015536:Down-Regulation / Q000235:genetics; D005091:Exons / Q000235:genetics; D006367:HeLa Cells; D006801:Humans; D007438:Introns / Q000235:genetics; D009154:Mutation / Q000235:genetics; D014176:Protein Biosynthesis / Q000235:genetics*; D012313:RNA / Q000235:genetics* / Q000378:metabolism*; D022821:RNA Splice Sites / Q000235:genetics; D012326:RNA Splicing / Q000235:genetics*; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000235:genetics; D014158:Transcription, Genetic / Q000235:genetics
D022821:RNA Splice Sites; D016693:Receptors, Antigen, T-Cell, alpha-beta; D012313:RNA