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Unspliced Precursors of NMD-Sensitive b-Globin Transcripts Exhibit Decreased Steady-State Levels in Erythroid Cells 1,3 ´ 1¤a 1,2 ´ 1,3¤b ´ ˜ 1,3 Ana Morgado , Fatima Almeida , Alexandre Teixeira , Ana Luısa Silva , Luısa Romao * ´ ´ ˜ ´ 1 Departamento de Genetica, Instituto Nacional de Saude Dr. Ricardo Jorge, Lisboa, Portugal, 2 Centro de Investigac¸ao em Genetica Molecular Humana, Faculdade de ˆ ´ ˆ Ciencias Medicas, Universidade Nova de Lisboa, Lisboa, Portugal, 3 BioFIG–Center for Biodiversity, Functional and Integrative Genomics, Faculdade de Ciencias, Universidade de Lisboa, Lisboa, Portugal Abstract Nonsense-mediated mRNA decay (NMD) is a quality control mechanism that detects and rapidly degrades mRNAs carrying premature translation-termination codons (PTCs). Mammalian NMD depends on both splicing and translation, and requires recognition of the premature stop codon by the cytoplasmic ribosomes. Surprisingly, some published data have suggested that nonsense codons may also affect the nuclear metabolism of the nonsense-mutated transcripts. To determine if nonsense codons could influence nuclear events, we have directly assessed the steady-state levels of the unspliced transcripts of wild-type and PTC-containing human b-globin genes stably transfected in mouse erythroleukemia (MEL) cells, after erythroid differentiati