Translation mediated by the nuclear cap-binding complex is confined to the perinuclear region via a CTIF-DDX19B interaction.

Newly synthesized mRNA is translated during its export through the nuclear pore complex, when its 5'-cap structure is still bound by the nuclear cap-binding complex (CBC), a heterodimer of cap-binding protein (CBP) 80 and CBP20. Despite its critical role in mRNA surveillance, the mechanism by which CBC-dependent translation (CT) is regulated remains unknown. Here, we demonstrate that the CT initiation factor (CTIF) is tethered in a translationally incompetent manner to the perinuclear region by the DEAD-box helicase 19B (DDX19B).

Eukaryotic initiation factor 4G suppresses nonsense-mediated mRNA decay by two genetically separable mechanisms.

Nonsense-mediated mRNA decay (NMD), which is best known for degrading mRNAs with premature termination codons (PTCs), is thought to be triggered by aberrant translation termination at stop codons located in an environment of the mRNP that is devoid of signals necessary for proper termination. In mammals, the cytoplasmic poly(A)-binding protein 1 (PABPC1) has been reported to promote correct termination and therewith antagonize NMD by interacting with the eukaryotic release factors 1 (eRF1) and 3 (eRF3). Using tethering assays in which proteins of interest are recruited as MS2 fusions to a NMD reporter transcript, we show that the three N-terminal RNA recognition motifs (RRMs) of PABPC1 are sufficient to antagonize NMD, while the eRF3-interacting C-terminal domain is dispensable.

eIF4E-bound mRNPs are substrates for nonsense-mediated mRNA decay in mammalian cells.

Eukaryotic mRNAs with premature translation termination codons (PTCs) are recognized and degraded through a process termed nonsense-mediated mRNA decay (NMD). The evolutionary conservation of the core NMD factors UPF1, UPF2 and UPF3 implies a similar basic mechanism of PTC recognition in all eukaryotes. However, while PTC-containing mRNAs in yeast seem to be available to NMD at each round of translation, mammalian NMD has been reported to be restricted to cap-binding complex (CBC)-bound mRNAs during the pioneer round of translation.

Nonsense-mediated mRNA decay - mechanisms of substrate mRNA recognition and degradation in mammalian cells.

The nonsense-mediated mRNA decay (NMD) pathway is well known as a translation-coupled quality control system that recognizes and degrades aberrant mRNAs with truncated open reading frames (ORF) due to the presence of a premature termination codon (PTC). However, a more general role of NMD in posttranscriptional regulation of gene expression is indicated by transcriptome-wide mRNA profilings that identified a plethora of physiological mRNAs as NMD targets. In this review, we focus on mechanistic aspects of target mRNA identification and degradation in mammalian cells, based on the available biochemical and genetic data, and point out knowledge gaps.

Imaging of congenital spine and spinal cord malformations.

This article reviews normal embryologic development of the spine and spinal cord and the imaging features of congenital abnormalities of the spine and spinal cord, with particular focus on magnetic resonance imaging. The authors discuss spinal dysraphisms, a heterogeneous group of congenital abnormalities of the spine and spinal cord, and provide information to expand understanding of these complex entities.