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Crosstalk between RNA metabolic pathways: an RNOMICS approach

Abstract

Eukaryotic cells contain many different RNA species. Nuclear pre-mRNAs and cytoplasmic mRNAs carry genomic information to the protein synthesis machinery, whereas many stable RNA species have important functional roles. The mature, functional forms of these RNA species are generated by post-transcriptional processing, and evidence has been accumulating that there are functional links between the various processing pathways. This indicates that there are regulatory networks that coordinate different stages of RNA metabolism. This article describes the aims and results, to date, of the European RNOMICS project as an example of an integrated approach to investigate these links.

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Figure 1: Interactions between proteins involved in different aspects of RNA metabolism.

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Acknowledgements

Research in the Beggs and Tollervey laboratories is mainly funded by grants from the Wellcome Trust and by an EC grant for the RNOMICS project.

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The authors declare no competing financial interests.

Related links

Related links

DATABASES

Saccharomyces Genome Database

Air1

Air2

Cbf5

Dcp1

Dcp2

Edc3

Gar1

Mtr4

Naf1

Nhp2

Nog2

Nop10

Pcf11

Rat1

Ssu72

Trf4

Trf5

Ydh1

Yhh1

FURTHER INFORMATION

RNOMICS

Hybrigenics SA

PROTEIN INTERACTION DATABASES

Biomolecular Interaction Network Database

Database of Interacting Proteins

IntAct

MINT — a Molecular Interactions database

Yeast GRID

TECHNOLOGIES AND TOOLS

EUROSCARF

HUPO Proteomics Standards Initiative

PIMWalker

GenoLink

Davidson College course notes on FRAP

Molecular Probes Invitrogen detection systems

Becker & Hickl GmbH Lifetime Imaging Techniques for Optical Microscopy

Glossary

FLUORESCENCE LIFETIME IMAGING MICROSCOPY (FLIM).

Fluorescence lifetime measurements can yield information on the molecular microenvironment of a fluorescent molecule. Factors such as the binding to macromolecules and the proximity of molecules that can deplete the excited state by FRET can all modify the lifetime of a fluorophore (see Becker & Hickl GmbH Lifetime Imaging Techniques for Optical Microscopy).

FLUORESCENCE RECOVERY AFTER PHOTOBLEACHING (FRAP).

A microscope technique used to measure the movement (for example, diffusion rates) of fluorescently tagged molecules over time in vivo. Specific regions in a cell are irreversibly photobleached using a laser; fluorescence is restored by diffusion of fluorescently tagged unbleached molecules into the bleached area (see Davidson College, Molecular Biology course notes on FRAP).

FLUORESCENCE RESONANCE ENERGY TRANSFER (FRET).

The non-radiative transfer of energy from a donor fluorophore to an acceptor fluorophore that is typically <80 Å away. FRET will only occur between fluorophores in which the emission spectrum of the donor has a significant overlap with the excitation of the acceptor. FRET can be used to detect the co-localization of proteins and other molecules with spatial resolution beyond the limits of conventional optical microscopy (see Molecular Probes Invitrogen detection systems).

SYNTHETIC-LETHAL SCREENS

When two yeast mutations are viable individually, but die when combined, they are described as being synthetic lethal. This genetic interaction indicates a functional relationship, either because they affect alternative pathways for a process, or because the gene products might be components of the same pathway or even of the same complex and the defects caused by the mutations are additive. Screening for mutations that are synthetic lethal with a mutation in a factor of interest might identify functionally related factors.

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Beggs, J., Tollervey, D. Crosstalk between RNA metabolic pathways: an RNOMICS approach. Nat Rev Mol Cell Biol 6, 423–429 (2005). https://doi.org/10.1038/nrm1648

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