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Nonsense-mediated mRNA decay (NMD) refers to the degradation of mRNA due to the presence of premature stop codon (PTC) on mRNA under pathological or physiological conditions. NMD is widely considered an mRNA-specific quality control process. Recently it was discovered that some PTCs do not trigger NMD in a variety of diseases - a process known as NMD escape; however, its exact mechanism remains unclear. At present, there are two widely accepted mechanistic hypotheses during NMD escape. The first is PTC read-through, in which protein translation undergoes PTC until the normal stop codon is encountered, producing a full-length protein. The second is translation reinitiation, in which protein translation recommences at the potential start codon downstream of PTC and terminates at the stop codon, producing an N-terminal truncated protein. Currently, an increasing number of drugs or small molecules that use PTC read-through have been successfully applied to treat nonsense variation-associated diseases. In this review, we summarize the NMD mechanism and discuss the application and progress in our understanding of NMD escape in disease therapy. This review should provide a useful framework to advance current understanding of the research and application of NMD escape.

Objective: To analyze the full nucleotide sequence of a null allele of major histocompatibility complex class I chain-related gene (MICA)., Methods: A sequence-based typing method was used to determine the nucleotide sequence of the MICA gene. Potential alleles were identified with a computer program., Results: The identified allele has possessed a sequence similar to that of MICA*027 except for a C→T substitution at position 184 in codon 62 (CAG→TAG) of exon 2. As a stop codon, this may result in a truncated protein., Conclusion: A null allele of MICA gene has been identified. The sequence has been submitted to the Genbank nucleotide sequence database (submission No. HWS10011131), which was officially named as MICA*063N by the WHO Nomenclature Committee in October 2010.

SV40 PolyA (Simian virus 40 PolyA, also called PolyA) sequence is DNA sequence (240 bp) that possesses the activity of transcription termination and can add PolyA tail to mRNA. PolyA contains AATAAA hexanucleotide polyadenylation signal. Fourteen copies of Alu in sense orientation (Alu14) were inserted downstream of GFP in pEGFP-C1 to construct pAlu14 plasmid, and then HeLa cells were transiently transfected with pAlu14. Northern blot and fluorescence microscope were used to observe GFP RNA and protein expressions. Our results found that Alu tandem sequence inhibited remarkably GFP gene expression, but produced higher-molecular-mass GFP fusion RNA. PolyA and its sequence that was deleted AATAAA signal in sense or antisense orientation were inserted between GFP and Alu tandem sequence in pAlu14. The results showed that all the inserted PolyA sequences partly eliminated the inhibition induced by Alu14. PolyA sequences without AATAAA signal in sense or antisense orientation still induced transcription termination. Antisense PolyA (PolyAas) was divided into four fragments that all are 60 bp long and the middle two fragments were named 2F2R and 3F3R. 2F2R or 3F3R was inserted upstream of Alu tandem sequence in pAlu14. The molecular mass of GFP fusion RNA increased when the copy number of 2F2R increased. 2F2R can support transcription elongation when 2F2R is located upstream of other 2F2R. Nevertheless, 2F2R located upstream of Alu tandem sequence can induce transcription termination. Inserting one copy or 64 copies of 3F3R in upstream of Alu tandem sequence caused the production of lower-molecular-mass GFP RNA.

Objective: To explore the pathogen and molecular basis of cryptogenic cirrhosis in a patient., Methods: Serum was collected from a patient, male, aged 56, with cryptogenic cirrhosis. HBV serologic markers were qualitatively tested, and HBsAg, HBeAg, and anti-HBc were quantitatively determined again. HBV DNA in serum was qualitatively tested using PCR, and quantified using fluorescence quantitative PCR. S gene was amplified, cloned, and sequenced., Results: HbsAg and anti-Hbe were negative, and anti-HBs, HBeAg, anti-HBc, and HBV DNA were all positive. HBsAg (S/N) was 0.77 (cutoff of S/N: >/= 2.00), HbeAg (S/N) was 56.43 (cutoff of S/N: >/= 2.10), anti-HBc (S/C(O)) was 0.03 (cutoff of S/C(O):