BACKGROUND In mammalian cells a regulatory mechanism, known as nonsense-mediated mRNA decay, degrades mRNA harboring premature termination codons. This mechanism is intron-dependent and functions as a quality control mechanism to eliminate abnormal transcripts and modulates the levels of a variety of naturally occurring transcripts. DESIGN AND METHODS In this study, we explored the molecular ...

We present an arc-consistency algorithm for a chain of lexicographic ordering constraints on m vectors of n variables each. The algorithm maintains arc-consistency and runs in O(nmd) time per invocation, where d is the cost of certain domain operations.

Elucidating the function of highly conserved regulatory sequences is a significant challenge in genomics today. Certain intragenic highly conserved elements have been associated with regulating levels of core components of the spliceosome and alternative splicing of downstream genes. Here we identify mutations in one such element, a regulatory alternative exon of SNRPB as the cause of cerebro-c...

OBJECTIVE To ascertain the relationship between the germline NF1 gene mutation and glioma development in patients with neurofibromatosis type 1 (NF1). METHODS The relationship between the type and location of the germline NF1 mutation and the presence of a glioma was analyzed in 37 participants with NF1 from one institution (Washington University School of Medicine [WUSM]) with a clinical dia...

mRNAs targeted by endonuclease decay generally disappear without detectable decay intermediates. The exception to this is nonsense-containing human β-globin mRNA, where the destabilization of full-length mRNA is accompanied by the cytoplasmic accumulation of 5'-truncated transcripts in erythroid cells of transgenic mice and in transfected erythroid cell lines. The relationship of the shortened ...

In mammals, Up-frameshift proteins (UPFs) form a surveillance complex that interacts with the exon junction complex (EJC) to elicit nonsense-mediated mRNA decay (NMD). UPF3b is the component of the surveillance complex that bridges the interaction with the EJC. Here, we report the 3.4 A resolution crystal structure of a minimal UPF3b-EJC assembly, consisting of the interacting domains of five p...

The ATP-dependent RNA helicase UPF1, a key factor in nonsense-mediated mRNA decay (NMD), was so far thought to be recruited specifically to NMD-targeted mRNAs by aberrantly terminating ribosomes. However, two recent publications reporting independently transcriptome-wide mapping of UPF1 occupancy on RNA challenge this model and instead provide evidence that UPF1 binds to mRNA already before tra...

Nonsense-mediated mRNA decay (NMD) is a cellular surveillance pathway that recognizes and degrades mRNAs with premature termination codons (PTCs). The mechanisms underlying translation termination are key to the understanding of RNA surveillance mechanisms such as NMD and crucial for the development of therapeutic strategies for NMD-related diseases. Here, we have used a fully reconstituted in ...

The nonsense-mediated mRNA decay (NMD) pathway is responsible for the rapid degradation of eukaryotic mRNAs on which ribosomes fail to terminate translation properly. NMD thereby contributes to the elimination of aberrant mRNAs, improving the fidelity of gene expression, but also serves to regulate gene expression at the post-transcriptional level. Here we discuss recent evidence as to how and ...

Cancer is a complex pathology involving different genes and cellular pathways. A combination of treatments with different targets is thus required to eliminate cancer cells. This review deals with a new potential therapeutic approach: inhibiting a single RNA degradation pathway so as to inhibit tumorigenesis by acting on different cellular processes and on the expression of various genes. Also ...