Human beta‐globin mRNAs that harbor a nonsense codon are degraded in murine erythroid tissues to intermediates lacking regions of exon I or exons I and II that have a cap‐like structure at the 5′ termini.

Previous studies have demonstrated that nonsense codons within beta zero‐thalassemic or in vitro‐mutagenized human beta‐globin transgenes result in the production of mRNAs that are degraded abnormally rapidly in the cytoplasm of murine erythroid cells. As a consequence, three RNA degradative intermediates are formed that lack sequences from either exon I or exons I and II. We show here that the intermediates, like the full‐length mRNA from which they derive and the endogenous murine beta maj‐globin mRNA, bind to the anticap monoclonal antibody H‐20 in a way that is competed by the cap analogue m7G and eliminated by prior exposure to tobacco acid pyrophosphatase. Furthermore, the intermediates, like the two full‐length mRNAs, are resistant to a 5′‐‐‐‐3′ exonuclease activity isolated from HeLa cell nuclei that degrades uncapped but not capped ribopolymers. Based on these observations, the intermediates appear to possess a structure that is indistinguishable from the cap at the 5′ end of mRNA, i.e. a methylated nucleoside that is linked to the RNA by a 5′‐5′ phosphodiester bond. Detection of the intermediates during murine development was concomitant with detection of full‐length thalassemic mRNA. Intermediate production appears to be influenced by RNA structure as indicated by the products that derive from a beta zero‐thalassemic beta‐globin transgene harboring a structural alteration (a 4 bp deletion) that was larger than any of those previously studied.