Decoding the non-coding RNAs in Alzheimer's disease.

Non-coding RNAs (ncRNAs) are integral components of biological networks with fundamental roles in regulating gene expression. They can integrate sequence information from the DNA code, epigenetic regulation and functions of multimeric protein complexes to potentially determine the epigenetic status and transcriptional network in any given cell. Humans potentially contain more ncRNAs than any other species, especially in the brain, where they may well play a significant role in human development and cognitive ability.

miRNA Effects on mRNA closed-loop formation during translation initiation.

A flurry of recent studies, carried out primarily in transfected cells or in vitro translation systems, have attempted to reveal the molecular means by which animal microRNAs (miRNAs) attenuate mRNA translation. Despite these intense efforts it has not yet been possible to derive a consensus model for such a mechanism. Here we summarise our own experimental contributions to this topic, which led us to propose that miRNAs control early translation initiation by affecting eukaryotic initiation factor 4E/cap structure and poly(A) tail function, and place them in a current context of this rapidly moving and challenging field.

Transcriptome-wide measurement of mRNA polyadenylation state.

The 3' poly(A) tail has important roles throughout the eukaryotic mRNA life cycle. A characteristic aspect of poly(A) tail function is furthermore that it can be modulated by changes in its length. This is in turn a well-recognised cellular means to regulate both, mRNA translation and stability, and a positive correlation has often been found between the efficiency of mRNA translation and the length of its poly(A) tail.

The ins and outs of translation.

A report on the 2nd EMBO Conference on Protein Synthesis and Translational Control, Heidelberg, Germany, 12-16 September 2007.

Methods to analyze microRNA-mediated control of mRNA translation.

MicroRNAs (miRs) are an important class of gene regulators that affect a wide range of biological processes. Despite the early recognition of miRs as translational regulators and intense interest in studying this phenomenon, it has so far not been possible to derive a consensus model for the underlying molecular mechanism(s). The potential of miRs to act in a combinatorial manner and to also promote mRNA decay creates conceptual and technical challenges in their study.

MicroRNAs control translation initiation by inhibiting eukaryotic initiation factor 4E/cap and poly(A) tail function.

MicroRNAs (miRNAs) repress translation of target mRNAs by interaction with partially mismatched sequences in their 3' UTR. The mechanism by which they act on translation has remained largely obscure. We examined the translation of mRNAs containing four partially mismatched miRNA-binding sites in the 3' UTR in HeLa cells cotransfected with a cognate miRNA.

Starting the protein synthesis machine: eukaryotic translation initiation.

The final assembly of the protein synthesis machinery occurs during translation initiation. This delicate process involves both ends of eukaryotic messenger RNAs as well as multiple sequential protein-RNA and protein-protein interactions. As is expected from its critical position in the gene expression pathway between the transcriptome and the proteome, translation initiation is a selective and highly regulated process.